開發環境應答型可注射生物啟發式水膠局部傳遞聚醯胺酸樹枝狀藥物載體於腫瘤之診斷及治療

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研究生：	Tefera Worku Mekonnen Tefera Worku Mekonnen
論文名稱：	開發環境應答型可注射生物啟發式水膠局部傳遞聚醯胺酸樹枝狀藥物載體於腫瘤之診斷及治療 Stimuli Responsive Injectable Bioinspired Hydrogels for the Local Delivery of Poly(amidoamine) Dendrimer Drug Carrier for Cancer Theragnostic Applications
指導教授：	蔡協致 Hsieh-Chih Tsai
口試委員:	- I-Ming Chu 蕭育生 Yu-Sheng Hsiao 何明樺 Ming-Hua Ho 陳玉暄 Yu-Shuan Chen 林宣因 Shuian-Yin Lin
學位類別：	博士 Doctor
系所名稱：	應用科技學院 - 應用科技研究所 Graduate Institute of Applied Science and Technology
論文出版年：	2021
畢業學年度：	109
語文別：	英文
論文頁數：	213
中文關鍵詞：	癌症治療、阿黴素、聚醯胺酸樹枝狀高分子、玻尿酸、卵清蛋白、脫氧膽酸鈉
外文關鍵詞：	Poly(amidoamine) dendrimer, Sodium deoxycholate
相關次數：	點閱：269 下載：0
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中文摘要
癌症是由體內細胞分裂異常引起的一種疾病。在癌症治療中，奈米粒子(NPs)在建立輸送藥物用以治療癌症上具有重要的作用。在眾多的奈米粒子當中，人們越來越關注於將氧化鐵奈米粒子(IO NPs)用於癌症生物醫學應用，此又稱為超順磁性奈米顆粒(SPIONs)。然而SPIONs的物化性質存在一些限制，為此有了開發具有生物安全傳遞的SPIONs的需求。目前的研究旨在開發能夠安全遞送且具有高癌症治療潛力的多功能單一或混合奈米粒子的生物材料。因此，合成了釓氧化鐵(GdIO)奈米粒子作為T1-T2雙峰顯影劑，並用於MRI追蹤藥物遞送。本研究採用鹼性共沉澱法製備4.5代聚醯胺酸樹枝狀高分子(G4.5PD)包覆著GdIO，在低頻交流磁場(LFAMF)作用下，於模擬胞內弱酸性環境(pH=5.0)中累積阿黴素的釋放量最高達77.47%。對T1和T2兩種核磁共振顯影劑進行體外比較，得到較好的弛緩率r1(5.19 mM-1s-1)和r2(26.13 mM-1s-1)。本文還設計以卵清蛋白(Oval)塗佈的氧化鐵(IO-Oval)和G4.5PD-順鉑奈米複合物(G4.5PD-Cisp NC)用於潛在的癌症化療與免疫治療，也研製了一種酶誘導交聯型玻尿酸水膠(HAc-Tyr-hyd)支架，用於遞送多功能的奈米粒子，透過與IO-Oval共培養於RAW 264.7和HaCaT細胞，可顯著的分泌促炎因子(TNF-α, IL-6)，而單純IO NPs處理的那些免疫細胞上IL-10分泌產生最大抑制，證明IO NPs在癌症治療中的具有免疫應答作用；論文中第三部分並著重探討新的藥物釋放途徑，將白藜蘆醇(RSV)與阿黴素(DOX)共同負載，以最大化其抗腫瘤作用，由於DOX在治療癌症方面的臨床應用受到劑量與相關副作用的限制，本文中利用一種在腫瘤細胞微環境pH值可原位注射的脫氧膽酸鈉水膠(Sd-DOC-hyd)，共負載DOX和RSV。藉由Sd-DOC-hyd誘導G4.5PD-DOX，證實RSV和DOX在協同抗腫瘤作用中的順序、控制和持續釋放具有協同抗腫瘤作用，並且在BALB / c裸鼠的HeLa細胞異種移植腫瘤，評估了Sd-DOC-hyd-RSV + G4.5PD-DOX的協同抗腫瘤活性。在此開發了在腫瘤細胞微環境中用於藥物的脫氧膽酸鈉和玻尿酸製成的水膠以及混合的多功能奈米粒子。在核磁共振引導的多模態癌症治療中，此生物啟發性水膠和多功能奈米粒子用以傳送抗癌藥物是安全具有效的治療方法
關鍵字：癌症治療、阿黴素、聚醯胺酸樹枝狀高分子、玻尿酸、卵清蛋白、脫氧膽酸鈉

Abstract
Cancer is a type of illness caused by abnormal cell division in the body. In cancer therapy, nanoparticles (NPs) have profound contributions in the development of effective and efficient biomaterials for cancer theragnostic. Out of the several types of NPs, there has been growing interest in the use of iron oxide nanoparticles (IO NPs) mainly known as superparamagnetic iron oxide nanoparticles (SPIONs) for several cancer biomedical applications. However, due some limitations associated to the physicochemical nature of the SPIONs, development of a novel biosafe delivery of SPIONs is highly demanding.
The current study aimed at to develop biomaterials for safe delivery of the multifunctional single or mixed NPs with limited or no side effects with a high cancer therapeutic potential. Thus, gadolinium iron oxide (GdIO) NPs have been synthesized as T1-T2 dual-modal contrast agents for MRI-guided drug delivery. A theragnostic GdIO encapsulated in a generation 4.5 poly(amidoamine) dendrimer (G4.5PD) was developed by alkaline coprecipitation method.
In the presence of a low frequency alternating magnetic field (LFAMF), a maximum cumulative doxorubicin (DOX) release of ~77.47% was achieved in mildly acidic simulated endosomal microenvironment (pH=5.0). Superior r1 (5.19 mM-1s-1) and r2 (26.13 mM-1s-1) relaxivity values were achieved for dual T1 and T2 MRI contrasting agent in vitro.
In this dissertation, we also designed to corroborates the immune-modulatory potential of ovalbumin (Oval) coated IO (IO-Oval) and G4.5PD-Cisplatin nanocomplex (G4.5PD-Cisp NC) for chemo-immunotherapy of cancer. An enzyme responsive injectable hyaluronic acid hydrogel (HAc-Tyr-hyd) scaffold for the delivery of the mixed multifunctional NPs has been developed, from the study a significant proinflammatory (TNF-α, IL-6) cytokines secretion was confirmed from the coincubation of RAW 264.7 immune cells with CAIO-Oval. Besides, the highest reduction of the secretion of IL-10 on those immune cells treated with bare CAIO NPs was observed, indicating the role of CAIO NPs in the immune response modulation in cancer treatment.
In one of the sections of this dissertation, we focused on maximizing the antitumor efficacy of doxorubicin (DOX) via coloading with resveratrol (RSV) using a new drug delivery approach. Due to the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and RSV using an injectable in situ formed sodium deoxycholate hydrogel (Sd-DOC-hyd) at the pH of tumor extracellular microenvironment. The sequential, controlled, and sustained release of RSV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5PD-DOX in the RSV-loaded Sd-DOC-hyd. The synergistic antitumor activity of Sd-DOC-hyd-RSV+G4.5PD-DOX was assessed on HeLa cells xenografted tumor in BALB/c nude mice. Therefore, bioinspired made hydrogel for the delivery of drugs as well as multifunctional NPs is a promising, safe, and effective approach for MRI guided multimodal cancer therapy.
Key words: Cancer therapy, Doxorubicin, poly(amidoamine) dendrimer, hyaluronic acid, Sodium deoxycholate

Table of Contents
Abstract (Chinese) 中文摘要    ....................................................i
Abstract    ..................................................................iii
Acknowledgment    ...................................................................vi
List of Figures    ..................................................................vii
List of Tables    .................................................................xxii
List of Schemes    ................................................................xxiii
Glossary of Definitions and Concepts    .........................................xxiv
List of Abbreviations and Acronyms    ..........................................xxv
CHAPTER ONE    ....................................................................1
Background    ....................................................................1
1. Statement of the Problems    ....................................................2
2. Objectives of the Study    ....................................................4
2.1. General Objective:    ....................................................4
2.2. Specific Objectives:    ....................................................4
3. Materials and Instruments    ....................................................4
3.1. Chemicals, Reagents, Animals and Cells    ....................................4
3.2. Instruments    ............................................................6
4. Soft Wares    ....................................................................7
5. Statistical Analysis    ....................................................7
CHAPTER TWO    ....................................................................8
Overview of Cancer    ............................................................8
1. Global Cancer Epidemiology    ....................................................8
1.1. The Etiology of Cancers    ...................................................10
1.2. Limitations of Conventional Cancer Therapies    ...........................11
2. The Applications of Nanoparticles in Conventional Therapies    ...........13
2.1 The Use of Nanoparticles to Target Cancer Cells    ...........................14
2.1.1. Nanoparticle for Passive Targeting    ...................................14
2.1.2. Nanoparticle for Active Targeting    ...................................15
2.2. Nanoparticle for Reversing the MDR in Cancer    ...........................15
2.3. Nanoparticle to Improve the Solubility of Cancer Therapeutics    ...........17
3. Multifunctional Magnetic Nanoparticles Improve Cancer Therapy    ...........18
4. Superparamagnetic Nanoparticles as Good Model for Cancer Theragnostic    ...19
4.1. Magnetite NPs for Targeted and Controlled Drug Release    ...................20
4.2. Magnetite for Hyperthermia Cancer Therapy    ...........................21
4.3. Magnetite for Cancer Immunotherapy    ...................................22
4.4. Magnetite NPs for MRI Diagnosis.    ...........................................23
5. Limitations of Magnetite (SPIONs) in Biomedical Applications    ...........24
6. Polymeric Nanocarriers    ...................................................25
6.1. Poly(amidoamine) Dendrimer    ...........................................25
6.2. The Unique Features of PAMAM Dendrimer    ...................................26
6.3. PH Responsiveness of PAMAM Dendrimer for Drug Delivery Applications    ...27
6.4. Cellular Internalization Mechanism of Poly(amidoamine) Dendrimer NPs    ...28
6.5. PAMAM Dendrimer for Encapsulation of Theragnostic Agents    ...................30
6.6. Limitations of PAMAM Dendrimer and Possible Solutions    ...................33
7. Bioinspired Materials for the Delivery of PAMAM Dendrimer Nano Carriers    ...33
7.1. Hyaluronic Acid Hydrogel    ...................................................34
7.2. Sodium Deoxycholate Hydrogel    ...........................................35
CHAPTER THREE    ...................................................................37
Encapsulation of Gadolinium Ferrite Nanoparticle in Generation 4.5 Poly (amidoamine) Dendrimer for Cancer Theragnostic Applications Using Low Frequency Alternating Magnetic Field    ...................................................37
1. Experimentations    ...........................................................40
1.1. Synthesis of G4.5PD-GdFe3O4 and G4.5PD-Fe3O4 NPs    ...........................40
1.2. Phantom MRI Relaxivity Studies    ...........................................40
1.3. Heat Generation Studies.    ...........................................41
1.4. DOX Encapsulation Study    ...................................................42
1.5. DOX Releasing Study    ...................................................42
1.6. In vitro Biocompatibility Study Using MTT Assay    ...........................44
1.7. In vitro Cellular Uptake Studies    ...........................................45
2. Results and Discussions    ...................................................46
2.1. Synthesis and Characterization of G4.5PD-GdIO and G4.5PD-IO NPs    ...........46
2.2. Phantom Relaxometric Studies of G4.5PD-GdIO and G4.5PD IO NPs.    ...........52
2.3. Magnetic Field Induced Heating Measurements.    ...........................53
2.4. Biocompatibility Using MTT Assay    ...........................................54
2.5. Drug Loading and Releasing Potential of G4.5PD-GdIO NPs    ...................55
2.6. Cancer Cell-Killing Efficacy of DOX Loaded G4.5PD-GdIO NPs    ...........57
2.7. Cellular Uptake Studies of G4.5PD-GdIO-DOX NP by Fluorescence Microscopy    ...59
3. Conclusions    ...........................................................60
CHAPTER FOUR    ...................................................................62
Stimuli Responsive Hyaluronic Acid Hydrogel for the Delivery of Poly(amidoamine)-Cisplatin Nanocomplex and Ovalbumin Coated Iron Oxide for Chemo-immunotherapy In vitro    ...........................................................................62
1. Experimentations    ...........................................................66
1.1. Syntheses of Iron oxide Nanoparticles    ...................................66
1.2. Preparation of Ovalbumin Coated CAIO NPs (CAIO-Oval)    ...................66
1.3. Preparation of Cisplatin Conjugated Generation 4.5 Poly(amidoamine) Dendrimer Nano-complex (G4.5PD-Cisp NC) and Cisplatin Releasing Studies    ...................67
1.3.1. Preparation of G4.5PD-Cisp NC    ...........................................67
1.3.2. Cisplatin Releasing Studies from G4.5PD-Cisp NC    ...................69
1.4. Synthesis of Hyaluronic Acid-Tyramine Conjugates (HAc-Tyr)    ...........70
1.5. Hydrogel Preparation from HAc-Tyr Conjugates    ...........................70
1.5.1. Rheological Studies of HAc-Tyr Hydrogel    ...........................71
1.5.2. The Morphological Characterization of HAc-Tyr Hydrogel Using FESEM.    ...72
1.5.3. The Swelling Rate Studies HAc-Tyr Hydrogel    ...........................72
1.5.4. The Enzymatic Degradation Studies of HAc-Tyr Hydrogel    ...................73
1.7. In vitro Cellular Uptake Studies of CAIO-Oval NPs and Effects on Immune Cells Responses    ...................................................................75
1.7.1. Cellular Uptake Studies of CAIO-Oval Using ICP-MS and Prussian Blue Staining.    ...................................................................75
1.7.2. In vitro Studies of the Effects of CAIO-Oval on Immune Cells    ...........76
1.8. Cellular Uptake and Apoptosis Study of G4.5PD-Cisp NC    ...................77
1.8.1. Cellular Uptake Study of G4.5PD-Cisp NC Using Flow Cytometry    ...........77
1.8.2. The Study of the Apoptotic Potential of G4.5PD-Cisp NC    ...................77
1.9. Encapsulation of CAIO NPs and G4.5PD-Cisp NC into HAc-Tyr Hydrogel and Releasing Studies    ...........................................................78
1.9.1. Encapsulation of CAIO-Oval NPs and G4.5PD-Cisp NC into HAc-Tyr Hydrogel    ...................................................................................78
1.9.2. Cisplatin Releasing Studies of HAc-Tyr-hyd+G4.5PD-Cisp    ...................79
2. Results and Discussions    ...................................................79
2.1. Syntheses and Characterization of Iron Oxide Nanoparticles (IONPs)    ...79
2.2. Preparation of Cisplatin Conjugated Generation 4.5 Poly(amidoamine) Dendrimer Nano-complex (G4.5PD-Cisp NC) and Cisplatin Releasing Studies    ...................86
2.2.1. Preparation of G4.5PD-Cisp NC    ...........................................86
2.2.2. Cisplatin Releasing Studies    ...........................................87
2.3. Synthesis of Hyaluronic Acid-Tyramine Conjugates (HAc-Tyr)    ...........88
2.4. Preparation and Characterization of HAc-Tyr Hydrogel    ...................89
2.4.1. Morphological Characterization of HAc-Tyr Hydrogel Using FESEM Study    ...92
2.4.2. HAc-Tyr Hydrogel Swelling Studies    ...................................94
2.4.3. HAc-Tyr Hydrogel Enzymatic Degradation Studies    ...........................95
2.5. In vitro Cytotoxicity and Anticancer Studies Using MTT Assay    ...........96
2.5.1 In vitro Cytotoxicity Study of HAc-Tyr Hydrogel and CAIO-Oval NPs    ...96
2.5.2. The Study of the Anticancer Effects of G4.5PD-Cisp NC    ...................97
2.6. In vitro CAIO-Oval NPs Cellular Uptake and Effects on Immune Cells    ...98
2.6.1. In vitro CAIO-Oval Cellular Uptake Study    ...........................98
2.6.2. In vitro Effects on RAW 264.7 Macrophages Cells Following Incubation with CAIO-Oval NPs.    ..................................................................100
2.7. Cellular Uptake and Apoptosis Study of G4.5PD-Cisp NC    ..................103
2.7.1. Cellular Uptake Study of G4.5PD-Cisp NC Using Flow Cytometry    ..........103
2.7.2. Apoptosis Study of G4.5PD-Cisp NC Study    ..........................104
2.8. Encapsulation of CAIO-Oval NPs and G4.5PD-Cisp NC into HAc-Tyr Hydrogel and Cisplatin Releasing Studies    ..................................................105
2.8.1. Co-encapsulation of CAIO-Oval NPs and G4.5PD-Cisp NC into HAc-Tyr Hydrogel    ..................................................................................106
2.8.2. Cisplatin Releasing Studies of HAc-Tyr-hyd+G4.5PD-Cisp NC    ..........106
3. Conclusions    ..........................................................107
CHAPTER FIVE    ..................................................................109
Bioinspired pH-Responsive Sodium Deoxycholate Hydrogel and PAMAM Dendrimer for Enhanced Cancer Therapy via Doxorubicin and Resveratrol Co-delivery    ..........109
1. Experimentations    ..........................................................112
1.1. Preparation of in-situ Sol-Gel Transformed Sodium Deoxycholate Hydrogel    ..112
1.1.1. Rheological Study of Sd-DOC-hyd    ..................................113
1.1.2. Morphological Characterization of Sd-DOC-hyd by FESEM Studies    ..........113
1.1.3. Sd-DOC-hyd X-ray Diffraction Studies    ..................................113
1.1.4. Swelling Ratio of Sd-DOC-hyd    ..........................................114
1.1.5. Degradation Study of Sd-DOC-hyd    ..................................114
1.2. Drug Loading and Releasing Studies    ..................................115
1.2.1. Doxorubicin Loading and Releasing Studies of G4.5 PAMAM Dendrimer    ..115
1.2.2. Co-encapsulation of G4.5PD-DOX and RSV into Sd-DOC-hyd    ..................115
1.2.3. Drug Releasing Studies of G4.5PD-DOX and Sd-DOC-hyd-RSV+G4.5PD-DOX    ..116
1.2.4. In vitro Biocompatibility Test of the Lyophilized Drug Carriers    ..117
1.2.5. Studies of Cellular Internalization of Drug Loaded Materials    ..........117
1.2. 6. Animal Experiment    ..................................................118
1.2.7. Histopathological Studies    ..........................................120
2. Results and Discussions    ..................................................121
2.1. Preparation and Characterizations of Sd-DOC-hyd    ..........................121
2.1.1. Rheological Study of the Sd-DOC-hyd    ..................................124
2.1.2. Microstructural Study of Sd-DOC-hyd Using XRD    ..........................126
2.1.3. FTIR Study of the Gelation of Sd-DOC Molecules    ..........................128
2.1.4. Sd-DOC-hyd Morphology Study Using FESEM    ..........................129
2.1.5. Swelling Ratio Study of Sd-DOC-hyd    ..................................131
2.1.6. Degradation Studies of Sd-DOC-hyd    ..................................132
2.2. Drug loading and Releasing Studies    ..................................133
2.2.1. Doxorubicin Loading and Releasing from G4.5 PAMAM Dendrimer    ..........133
2.2.2. Drugs Releasing Studies from Sd-DOC-hyd-RSV+G4.5-DOX    ..................134
2.3. In vitro Biocompatibility Test    ..........................................136
2.4. The Cellular Uptake Studies of G4.5PD-DOX and Sd-DOC-hyd-RSV    ..........137
2.5. In vivo Antitumor Study of Sd-DOC-hyd-RSV+G4.5PD-DOX    ..................139
2.6. Histopathological Studies Analysis Based on Samples Collected from Major Internal Organs    ..................................................................144
3. Conclusions    ..........................................................149
CHAPTER SIX    ..................................................................150
General Summary    ..........................................................150
1. Recommendations and Future Prospective    ..................................153
CHAPTER SEVEN    ..................................................................155
References:    ..................................................................155
APPENDIX    ..................................................................178
1. Supporting files    ..........................................................178
2. Publications    ..........................................................183



                                

7. References:
1. Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2016. CA Cancer J Clin, 2016. 66(1): p. 7-30.
2. Sambi, M., L. Bagheri, and M.R. Szewczuk, Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates. J Oncol, 2019. 2019: p. 4508794.
3. Sannino, A., C. Demitri, and M. Madaghiele, Biodegradable Cellulose-based Hydrogels: Design and Applications. Materials, 2009. 2(2): p. 353-373.
4. Tayo, L.L.J.B.r., Stimuli-responsive nanocarriers for intracellular delivery. Biophys Rev, 2017. 9(6): p. 931-940.
5. Sun, W., et al., Dendrimer-based magnetic iron oxide nanoparticles: their synthesis and biomedical applications. Drug Discov Today, 2016. 21(12): p. 1873-1885.
6. Wang, Y., et al., Stable and pH-responsive polyamidoamine based unimolecular micelles capped with a zwitterionic polymer shell for anticancer drug delivery. RSC Advances, 2016. 6(21): p. 17728-17739.
7. Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2019. CA Cancer J Clin, 2019. 69(1): p. 7-34.
8. Kuo, C.N., et al., Cancers in Taiwan: Practical insight from epidemiology, treatments, biomarkers, and cost. J Formos Med Assoc, 2020. 119(12): p. 1731-1741.
9. Chen, D.S. and I. Mellman, Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013. 39(1): p. 1-10.
10. Andersen, M.H., et al., Cancer treatment: the combination of vaccination with other therapies. Cancer Immunol Immunother, 2008. 57(11): p. 1735-43.
11. Gobbo, O.L., et al., Magnetic Nanoparticles in Cancer Theranostics. Theranostics, 2015. 5(11): p. 1249-63.
12. Islami, F., K.D. Miller, and A. Jemal, Cancer burden in the United States—a review. Annals of Cancer Epidemiology, 2018. 1: p. 1-1.
13. Sato, Y., et al., Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment. Cancer Microenviron, 2009. 2 Suppl 1: p. 205-14.
14. Sau, S., et al., Multifunctional nanoparticles for cancer immunotherapy: A groundbreaking approach for reprogramming malfunctioned tumor environment. J Control Release, 2018. 274: p. 24-34.
15. Tran, L., et al., Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res, 2017. 5(12): p. 1141-1151.
16. Thorn, C.F., et al., Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics, 2011. 21(7): p. 440-6.
17. McKean, M.A. and R.N. Amaria, Multidisciplinary treatment strategies in high-risk resectable melanoma: Role of adjuvant and neoadjuvant therapy. Cancer Treat Rev, 2018. 70: p. 144-153.
18. Quesnel, B., X. Thuru, and C. Bailly, Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times. NAR Cancer, 2020. 2(1).
19. Rotolo, F., et al., Adjuvant cisplatin-based chemotherapy in nonsmall-cell lung cancer: new insights into the effect on failure type via a multistate approach. Ann Oncol, 2014. 25(11): p. 2162-2166.
20. Saeed, M., W. Ren, and A. Wu, Therapeutic applications of iron oxide based nanoparticles in cancer: basic concepts and recent advances. Biomater Sci, 2018. 6(4): p. 708-725.
21. Zhuang, J., et al., Nanoparticle Delivery of Immunostimulatory Agents for Cancer Immunotherapy. Theranostics, 2019. 9(25): p. 7826-7848.
22. Zhu, X.M., et al., Enhanced cellular uptake of aminosilane-coated superparamagnetic iron oxide nanoparticles in mammalian cell lines. Int J Nanomedicine, 2012. 7: p. 953-64.
23. Zhao, S., et al., Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics. Theranostics, 2020. 10(14): p. 6278-6309.
24. Krasia-Christoforou, T. and T.K. Georgiou, Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy. Journal of Materials Chemistry B, 2013. 1(24).
25. Ma, Y.Y., et al., Molecular Imaging of Cancer with Nanoparticle-Based Theranostic Probes. Contrast Media Mol Imaging, 2017. 2017: p. 1026270.
26. Xie, J. and S. Jon, Magnetic nanoparticle-based theranostics. Theranostics, 2012. 2: p. 122-4.
27. Xie, J., S. Lee, and X. Chen, Nanoparticle-based theranostic agents. Adv Drug Deliv Rev, 2010. 62(11): p. 1064-79.
28. Ray, S., et al., Dendrimer- and copolymer-based nanoparticles for magnetic resonance cancer theranostics. Theranostics, 2018. 8(22): p. 6322-6349.
29. Tayo, L.L., Stimuli-responsive nanocarriers for intracellular delivery. Biophys Rev, 2017. 9(6): p. 931-940.
30. Zhang, C., et al., Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies. Asia Pac J Clin Oncol, 2016. 12(1): p. 13-21.
31. Yen, S.K., P. Padmanabhan, and S.T. Selvan, Multifunctional iron oxide nanoparticles for diagnostics, therapy and macromolecule delivery. Theranostics, 2013. 3(12): p. 986-1003.
32. Vinardell, M.P. and M.J.N. Mitjans, Antitumor activities of metal oxide nanoparticles. 2015. 5(2): p. 1004-1021.
33. Farokhzad, O.C. and R. Langer, Nanomedicine: developing smarter therapeutic and diagnostic modalities. Adv Drug Deliv Rev, 2006. 58(14): p. 1456-9.
34. Portney, N.G. and M. Ozkan, Nano-oncology: drug delivery, imaging, and sensing. Anal Bioanal Chem, 2006. 384(3): p. 620-30.
35. Wang, Y., et al., Production of Transgenic Mice Through Sperm-Mediated Gene Transfer Using Magnetic Nano-Carriers. J Biomed Nanotechnol, 2017. 13(12): p. 1673-1681.
36. Jung, H., et al., Dual MRI T1 and T2(*) contrast with size-controlled iron oxide nanoparticles. Nanomedicine, 2014. 10(8): p. 1679-89.
37. Chen, Z., et al., Synthesis, functionalization, and nanomedical applications of functional magnetic nanoparticles. Chinese Chemical Letters, 2018. 29(11): p. 1601-1608.
38. Wang, Y.X., Superparamagnetic iron oxide based MRI contrast agents: Current status of clinical application. Quant Imaging Med Surg, 2011. 1(1): p. 35-40.
39. Wahajuddin and S. Arora, Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int J Nanomedicine, 2012. 7: p. 3445-71.
40. Wahab, R., F. Khan, and A.A. Al-Khedhairy, Hematite iron oxide nanoparticles: apoptosis of myoblast cancer cells and their arithmetical assessment. RSC Advances, 2018. 8(44): p. 24750-24759.
41. Wolf-Grosse, S., et al., Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model. Int J Nanomedicine, 2017. 12: p. 3927-3940.
42. Zanganeh, S., et al., Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol, 2016. 11(11): p. 986-994.
43. Grosse, S., J. Stenvik, and A.M. Nilsen, Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes. Int J Nanomedicine, 2016. 11: p. 4625-4642.
44. Sk, U.H. and C. Kojima, Dendrimers for theranostic applications. Biomol Concepts, 2015. 6(3): p. 205-17.
45. Lyu, Z., et al., Poly(amidoamine) dendrimers: covalent and supramolecular synthesis. Materials Today Chemistry, 2019. 13: p. 34-48.
46. Krasia-Christoforou, T. and T.K.J.J.o.M.C.B. Georgiou, Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy. Journal of Materials Chemistry B, 2013. 1(24): p. 3002-3025.
47. Kesharwani, P., K. Jain, and N.K.J.P.i.P.S. Jain, Dendrimer as nanocarrier for drug delivery. Progress in Polymer Science, 2014. 39(2): p. 268-307.
48. Min, J.B., et al., Preparation, characterization, and cellular uptake of resveratrol-loaded trimethyl chitosan nanoparticles. Food Sci Biotechnol, 2018. 27(2): p. 441-450.
49. Araujo, R.V., et al., New Advances in General Biomedical Applications of PAMAM Dendrimers. Molecules, 2018. 23(11).
50. Fang, R., et al., Encapsulation of ultrafine metal-oxide nanoparticles within mesopores for biomass-derived catalytic applications. Chem Sci, 2018. 9(7): p. 1854-1859.
51. Patil, R.M., et al., Comprehensive cytotoxicity studies of superparamagnetic iron oxide nanoparticles. Biochem Biophys Rep, 2018. 13: p. 63-72.
52. Shadrack, D.M., E.B. Mubofu, and S.S. Nyandoro, Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement. Int J Mol Sci, 2015. 16(11): p. 26363-77.
53. Walle, T., Bioavailability of resveratrol. Ann N Y Acad Sci, 2011. 1215: p. 9-15.
54. Sarkar, K. and H. Yang, Encapsulation and extended release of anti-cancer anastrozole by stealth nanoparticles. Drug Deliv, 2008. 15(5): p. 343-6.
55. Lima-Tenorio, M.K., et al., Magnetic nanoparticles: In vivo cancer diagnosis and therapy. Int J Pharm, 2015. 493(1-2): p. 313-27.
56. Kim, J.-H., et al., Polymers for bioimaging. Progress in Polymer Science, 2007. 32(8-9): p. 1031-1053.
57. Li, J., et al., Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. Int J Pharm, 2018. 546(1-2): p. 215-225.
58. Chen, K.J., et al., A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity. Biomaterials, 2011. 32(8): p. 2160-5.
59. Chang, Y., et al., Dendrimer functionalized water soluble magnetic iron oxide conjugates as dual imaging probe for tumor targeting and drug delivery. Polym. Chem., 2013. 4(3): p. 789-794.
60. Chang, Y., et al., Novel water-soluble and pH-responsive anticancer drug nanocarriers: doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs). J Colloid Interface Sci, 2011. 363(1): p. 403-9.
61. Chang, Y., et al., Synthesis and characterization of DOX-conjugated dendrimer-modified magnetic iron oxide conjugates for magnetic resonance imaging, targeting, and drug delivery. Journal of Materials Chemistry, 2012. 22(19).
62. Yalcin, S., et al., Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines. Biomed Pharmacother, 2014. 68(6): p. 737-43.
63. Pan, B., et al., Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system. Cancer Res, 2007. 67(17): p. 8156-63.
64. Wu, X., et al., Water-soluble dendritic-linear triblock copolymer-modified magnetic nanoparticles: preparation, characterization and drug release properties. Journal of Materials Chemistry, 2011. 21(35).
65. Zhu, J., et al., Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells. RSC Advances, 2015. 5(38): p. 30286-30296.
66. Taratula, O., et al., Multifunctional Nanomedicine Platform for Cancer Specific Delivery of siRNA by Superparamagnetic Iron Oxide Nanoparticles-Dendrimer Complexes. Current Drug Delivery, 2011. 8(1): p. 59-69.
67. Tan, M., et al., Synthesis and evaluation of a targeted nanoglobular dual-modal imaging agent for MR imaging and image-guided surgery of prostate cancer. Pharm Res, 2014. 31(6): p. 1469-76.
68. Wang, Q., et al., Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer. Int J Nanomedicine, 2015. 10: p. 4479-90.
69. Menon, J.U., K.T.J.R.i.N. Nguyen, and Nanotechnology, Polymer-coated magnetic nanoparticles for cancer diagnosis and therapy. Rev. Nanosci. Nanotechnol., 2012. 1(4): p. 284-297.
70. Wang, Y., et al., Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics. Soft Matter, 2020. 16(20): p. 4756-4766.
71. Park, K.M., D. Lewis, and S. Gerecht, Bioinspired Hydrogels to Engineer Cancer Microenvironments. Annu Rev Biomed Eng, 2017. 19: p. 109-133.
72. Li, X.C., et al., Bioinspired Hydrogel-Polymer Hybrids with a Tough and Antifatigue Interface via One-Step Polymerization. ACS Appl Mater Interfaces, 2020. 12(45): p. 51036-51043.
73. Scodeller, P., Hyaluronidase and other Extracellular Matrix Degrading Enzymes for Cancer Therapy: New Uses and Nano-Formulations. Journal of Carcinogenesis & Mutagenesis, 2014. 05(04).
74. Fallacara, A., et al., Hyaluronic Acid in the Third Millennium. Polymers (Basel), 2018. 10(7).
75. Fan, Z., et al., Bienzymatically crosslinked gelatin/hyaluronic acid interpenetrating network hydrogels: preparation and characterization. RSC Advances, 2015. 5(3): p. 1929-1936.
76. Babu, P., N.M. Sangeetha, and U. Maitra, Supramolecular Chemistry of Bile Acid Derivatives: Formation of Gels. Macromolecular Symposia, 2006. 241(1): p. 60-67.
77. McNeel, K.E., et al., Sodium deoxycholate/TRIS-based hydrogels for multipurpose solute delivery vehicles: Ambient release, drug release, and enantiopreferential release. Talanta, 2018. 177: p. 66-73.
78. McNeel, K.E., et al., Sodium Deoxycholate Hydrogels: Effects of Modifications on Gelation, Drug Release, and Nanotemplating. J Phys Chem B, 2015. 119(27): p. 8651-9.
79. Maity, M. and U. Maitra, Supramolecular Gels from Conjugates of Bile Acids and Amino Acids and Their Applications. European Journal of Organic Chemistry, 2017. 2017(13): p. 1713-1720.
80. Tschulik, K. and R.G. Compton, Nanoparticle impacts reveal magnetic field induced agglomeration and reduced dissolution rates. Phys Chem Chem Phys, 2014. 16(27): p. 13909-13.
81. Wadajkar, A.S., J.U. Menon, and K.T. Nguyen, Polymer-Coated Magnetic Nanoparticles for Cancer Diagnosis and Therapy. Reviews in Nanoscience and Nanotechnology, 2012. 1(4): p. 284-297.
82. Andrgie, A.T., et al., Non-Anticoagulant Heparin Prodrug Loaded Biodegradable and Injectable Thermoresponsive Hydrogels for Enhanced Anti-Metastasis Therapy. Macromol Biosci, 2019: p. e1800409.
83. Noriega-Luna, B., et al., Applications of Dendrimers in Drug Delivery Agents, Diagnosis, Therapy, and Detection. Journal of Nanomaterials, 2014. 2014: p. 1-19.
84. Han, X., et al., Applications of nanoparticles in biomedical imaging. Nanoscale, 2019. 11(3): p. 799-819.
85. Addisu, K.D., et al., Bioinspired, Manganese-Chelated Alginate-Polydopamine Nanomaterials for Efficient in Vivo T1-Weighted Magnetic Resonance Imaging. ACS Appl Mater Interfaces, 2018. 10(6): p. 5147-5160.
86. Anbazhagan, R., et al., MoS2-Gd Chelate Magnetic Nanomaterials with Core-Shell Structure Used as Contrast Agents in in Vivo Magnetic Resonance Imaging. ACS Appl Mater Interfaces, 2016. 8(3): p. 1827-35.
87. Xiao, Y.D., et al., MRI contrast agents: Classification and application (Review). Int J Mol Med, 2016. 38(5): p. 1319-1326.
88. Lodhia, J., et al., Development and use of iron oxide nanoparticles (Part 1): Synthesis of iron oxide nanoparticles for MRI. Biomed Imaging Interv J, 2010. 6(2): p. e12.
89. Yu, S., et al., Magnetic and pH-sensitive nanoparticles for antitumor drug delivery. Colloids Surf B Biointerfaces, 2013. 103: p. 15-22.
90. Prasannan, A., et al., Synthesis and evaluation of the targeted binding of RGD-containing PEGylated-PEI/DNA polyplex micelles as radiotracers for a tumor-targeting imaging probe. RSC Advances, 2015. 5(130): p. 107455-107465.
91. Hua, X., et al., Magnetically triggered drug release from nanoparticles and its applications in anti-tumor treatment. Drug Deliv, 2017. 24(1): p. 511-518.
92. Mekuria, S.L., T.A. Debele, and H.C. Tsai, Encapsulation of Gadolinium Oxide Nanoparticle (Gd2O3) Contrasting Agents in PAMAM Dendrimer Templates for Enhanced Magnetic Resonance Imaging in Vivo. ACS Appl Mater Interfaces, 2017. 9(8): p. 6782-6795.
93. Baykal, A., et al., Synthesis and Characterization of Dendrimer-Encapsulated Iron and Iron-Oxide Nanoparticles. Journal of Superconductivity and Novel Magnetism, 2012. 25(5): p. 1541-1549.
94. Cheng, K.W. and S.H. Hsu, A facile method to prepare superparamagnetic iron oxide and hydrophobic drug-encapsulated biodegradable polyurethane nanoparticles. Int J Nanomedicine, 2017. 12: p. 1775-1789.
95. Drake, P., et al., Gd-doped iron-oxide nanoparticles for tumour therapy via magnetic field hyperthermia. Journal of Materials Chemistry, 2007. 17(46).
96. Rouhollah, K., et al., Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles. J Pharm Sci, 2013. 102(6): p. 1825-1835.
97. Wu, J., et al., Magnetic targeted drug delivery carriers encapsulated with pH-sensitive polymer: synthesis, characterization and in vitro doxorubicin release studies. J Biomater Sci Polym Ed, 2016. 27(13): p. 1303-16.
98. Zou, H. and W. Yuan, Temperature- and redox-responsive magnetic complex micelles for controlled drug release. Journal of Materials Chemistry B, 2015. 3(2): p. 260-269.
99. Chandra, S., et al., Dendrimer–Doxorubicin conjugate for enhanced therapeutic effects for cancer. Journal of Materials Chemistry, 2011. 21(15).
100. Hayashi, K., et al., High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect. ACS Appl Mater Interfaces, 2010. 2(7): p. 1903-11.
101. Xue, W., et al., AMF responsive DOX-loaded magnetic microspheres: transmembrane drug release mechanism and multimodality postsurgical treatment of breast cancer. Journal of Materials Chemistry B, 2018. 6(15): p. 2289-2303.
102. Hailemeskel, B.Z., et al., Synthesis and characterization of diselenide linked poly(ethylene glycol) nanogel as multi-responsive drug carrier. Applied Surface Science, 2018. 449: p. 15-22.
103. Cui, C., et al., Cellular uptake, intracellular trafficking, and antitumor efficacy of doxorubicin-loaded reduction-sensitive micelles. Biomaterials, 2013. 34(15): p. 3858-69.
104. Quan, Q., et al., HSA coated iron oxide nanoparticles as drug delivery vehicles for cancer therapy. Mol Pharm, 2011. 8(5): p. 1669-76.
105. Birhan, Y.S., et al., Fabrication of redox-responsive Bi(mPEG-PLGA)-Se2 micelles for doxorubicin delivery. Int J Pharm, 2019. 567: p. 118486.
106. Fu, F., et al., Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: investigating the role played by PEG spacer. ACS Appl Mater Interfaces, 2014. 6(18): p. 16416-25.
107. Strable, E., et al., Synthesis and characterization of soluble iron oxide-dendrimer composites. Chemistry of Materials, 2001. 13(6): p. 2201-2209.
108. Shanthi, K., et al., Fabrication of a pH responsive DOX conjugated PEGylated palladium nanoparticle mediated drug delivery system: an in vitro and in vivo evaluation. RSC Advances, 2015. 5(56): p. 44998-45014.
109. Tajabadi, M., M.E. Khosroshahi, and S. Bonakdar, An efficient method of SPION synthesis coated with third generation PAMAM dendrimer. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013. 431: p. 18-26.
110. Xu, W., et al., Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine. Sci Rep, 2013. 3: p. 3210.
111. Zhang, H., et al., Synthesis and characterization of Gd-doped magnetite nanoparticles. Journal of Magnetism and Magnetic Materials, 2017. 423: p. 386-394.
112. Farghali1, M.A., El-Din,T.A.S., Al-Enizi,A.M., El Bahnasawy,R.M., Graphene/ Magnetite Nanocomposite for Potential Environmental Application. Int. J. Electrochem. Sci., 2015. 10: p. 529 - 537.
113. Cao, D., et al., High saturation magnetization of gamma-Fe2O3 nano-particles by a facile one-step synthesis approach. Sci Rep, 2016. 6: p. 32360.
114. Thorat, N.D., et al., Superparamagnetic Gadolinium Ferrite Nanoparticles with Controllable Curie Temperature - Cancer Theranostics for MR-Imaging-Guided Magneto-Chemotherapy. European Journal of Inorganic Chemistry, 2016. 2016(28): p. 4586-4597.
115. Zhang, G., et al., Gadolinium-Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System. Advanced Functional Materials, 2015. 25(38): p. 6101-6111.
116. Aghazadeh, M., et al., Gd3+ doped Fe3O4 nanoparticles with proper magnetic and supercapacitive characteristics: A novel synthesis platform and characterization. Korean Journal of Chemical Engineering, 2018. 35(6): p. 1341-1347.
117. Thorat, N.D., et al., Multi-modal MR imaging and magnetic hyperthermia study of Gd doped Fe3O4 nanoparticles for integrative cancer therapy. RSC Advances, 2016. 6(97): p. 94967-94975.
118. Xiao, N., et al., T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles. J Colloid Interface Sci, 2014. 417: p. 159-65.
119. Kattel, K., et al., A facile synthesis, in vitro and in vivo MR studies of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential MRI contrast agent. ACS Appl Mater Interfaces, 2011. 3(9): p. 3325-34.
120. Douglas, F.J., et al., Gadolinium-doped magnetite nanoparticles from a single-source precursor. RSC Advances, 2016. 6(78): p. 74500-74505.
121. Singh, G., et al., Synthesis of gadolinium oxide nanodisks and gadolinium doped iron oxide nanoparticles for MR contrast agents. Journal of Materials Chemistry B, 2017. 5(3): p. 418-422.
122. Wang, K., et al., Gadolinium-labelled iron/iron oxide core/shell nanoparticles as T1–T2 contrast agent for magnetic resonance imaging. RSC Advances, 2018. 8(47): p. 26764-26770.
123. Ahmad, M.W., et al., Potential dual imaging nanoparticle: Gd2O3 nanoparticle. Sci Rep, 2015. 5: p. 8549.
124. Xu, W., et al., Paramagnetic nanoparticle T1 and T2 MRI contrast agents. Phys Chem Chem Phys, 2012. 14(37): p. 12687-700.
125. Zhang, W., et al., Surface impact on nanoparticle-based magnetic resonance imaging contrast agents. Theranostics, 2018. 8(9): p. 2521-2548.
126. Fang, J., et al., Extremely low frequency alternating magnetic field-triggered and MRI-traced drug delivery by optimized magnetic zeolitic imidazolate framework-90 nanoparticles. Nanoscale, 2016. 8(6): p. 3259-63.
127. Yao, J., J. Feng, and J. Chen, External-stimuli responsive systems for cancer theranostic. Asian Journal of Pharmaceutical Sciences, 2016. 11(5): p. 585-595.
128. Debele, T.A., S. Peng, and H.C. Tsai, Drug Carrier for Photodynamic Cancer Therapy. Int J Mol Sci, 2015. 16(9): p. 22094-136.
129. Venugopal I.; Pernal, S.D., A.; Bentley, J.; Engelhard,H. and Linninger, A., Magnetic field-enhanced cellular uptake of doxorubicin-loaded magnetic nanoparticles for tumor treatment. Mater. Res. Express, 2016: p. 1-23.
130. Behzadi, S., et al., Cellular uptake of nanoparticles: journey inside the cell. Chem Soc Rev, 2017. 46(14): p. 4218-4244.
131. Tsai, H.C., et al., Two-photon confocal imaging study: cell uptake of two photon dyes-labeled PAMAM dendrons in HeLa cells. J Biomed Mater Res A, 2012. 100(3): p. 746-56.
132. Speelmans, G., et al., Transport of the anti-cancer drug doxorubicin across cytoplasmic membranes and membranes composed of phospholipids derived from Escherichia coli occurs via a similar mechanism. Biochim Biophys Acta, 1996. 1284(2): p. 240-6.
133. Bolhassani, A., S. Safaiyan, and S. Rafati, Improvement of different vaccine delivery systems for cancer therapy. Mol Cancer, 2011. 10: p. 3.
134. Wang, X., et al., Advances of cancer therapy by nanotechnology. Cancer Res Treat, 2009. 41(1): p. 1-11.
135. Reichel, D., M. Tripathi, and J.M. Perez, Biological Effects of Nanoparticles on Macrophage Polarization in the Tumor Microenvironment. Nanotheranostics, 2019. 3(1): p. 66-88.
136. Dukhinova, M.S., et al., Metal Oxide Nanoparticles in Therapeutic Regulation of Macrophage Functions. Nanomaterials (Basel), 2019. 9(11).
137. Dulinska-Litewka, J., et al., Superparamagnetic Iron Oxide Nanoparticles-Current and Prospective Medical Applications. Materials (Basel), 2019. 12(4).
138. Edwardson, D.W., et al., Inflammatory cytokine production in tumor cells upon chemotherapy drug exposure or upon selection for drug resistance. PLoS One, 2017. 12(9): p. e0183662.
139. Emens, L.A., Chemoimmunotherapy. Cancer J, 2010. 16(4): p. 295-303.
140. Enriquez Perez, J., et al., The effect of locally delivered cisplatin is dependent on an intact immune function in an experimental glioma model. Sci Rep, 2019. 9(1): p. 5632.
141. Kim, W.S., et al., Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2- and Tr1-biased T-cell immunity. Oncotarget, 2016. 7(23): p. 33765-82.
142. Dasari, S. and P.B. Tchounwou, Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol, 2014. 740: p. 364-78.
143. Laumet, G., et al., Cisplatin educates CD8+ T cells to prevent and resolve chemotherapy-induced peripheral neuropathy in mice. Pain, 2019. 160(6): p. 1459-1468.
144. Shen, C.-C., et al., A single exposure to iron oxide nanoparticles attenuates antigen-specific antibody production and T-cell reactivity in ovalbumin-sensitized BALB/c mice. 2011. 6: p. 1229.
145. Zhu, L., et al., Alginate Particles with Ovalbumin (OVA) Peptide Can Serve as a Carrier and Adjuvant for Immune Therapy in B16-OVA Cancer Model. Med Sci Monit Basic Res, 2017. 23: p. 166-172.
146. Singh, D., et al., Citric acid coated magnetic nanoparticles: Synthesis, characterization and application in removal of Cd(II) ions from aqueous solution. Journal of Water Process Engineering, 2014. 4: p. 233-241.
147. Dheyab, M.A., et al., Simple rapid stabilization method through citric acid modification for magnetite nanoparticles. Sci Rep, 2020. 10(1): p. 10793.
148. Kang, S., et al., Effects of gold nanoparticle-based vaccine size on lymph node delivery and cytotoxic T-lymphocyte responses. J Control Release, 2017. 256: p. 56-67.
149. Kurisawa, M., et al., Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering. Chem Commun (Camb), 2005(34): p. 4312-4.
150. Feng, Q., et al., Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci Rep, 2018. 8(1): p. 2082.
151. Cowger, T.A., et al., Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging. Theranostics, 2015. 5(11): p. 1225-32.
152. Sherwood, J., et al., Shape-dependent cellular behaviors and relaxivity of iron oxide-based T1 MRI contrast agents. Nanoscale, 2016. 8(40): p. 17506-17515.
153. Li, M., H. Gu, and C. Zhang, Highly sensitive magnetite nano clusters for MR cell imaging. Nanoscale Res Lett, 2012. 7(1): p. 204.
154. St Germain, C., et al., Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3. Neoplasia, 2010. 12(7): p. 527-38.
155. Yu, S., et al., Albumin-coated SPIONs: an experimental and theoretical evaluation of protein conformation, binding affinity and competition with serum proteins. Nanoscale, 2016. 8(30): p. 14393-405.
156. Vismara, E., et al., Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications. Molecules, 2017. 22(7).
157. Racuciu, M., D.E. Creanga, and A. Airinei, Citric-acid-coated magnetite nanoparticles for biological applications. Eur Phys J E Soft Matter, 2006. 21(2): p. 117-21.
158. Bergmann Cp, P.P.C., Raman Spectroscopy of Iron Oxide of Nanoparticles (Fe3O4). Journal of Material Science & Engineering, 2015. 05(01).
159. Jubb, A.M. and H.C. Allen, Vibrational Spectroscopic Characterization of Hematite, Maghemite, and Magnetite Thin Films Produced by Vapor Deposition. ACS Applied Materials & Interfaces, 2010. 2(10): p. 2804-2812.
160. Shebanova, O.N. and P. Lazor, Raman study of magnetite (Fe3O4): laser-induced thermal effects and oxidation. Journal of Raman Spectroscopy, 2003. 34(11): p. 845-852.
161. Gunawardana, B., N. Singhal, and P. Swedlund, Degradation of Chlorinated Phenols by Zero Valent Iron and Bimetals of Iron: A Review. Environmental Engineering Research, 2011. 16(4): p. 187-203.
162. Sattarahmady, N., et al., Albumin coated arginine-capped magnetite nanoparticles as a paclitaxel vehicle: Physicochemical characterizations and in vitro evaluation. Journal of Drug Delivery Science and Technology, 2016. 36: p. 68-74.
163. Singh, G., et al., Synthesis of gadolinium oxide nanodisks and gadolinium doped iron oxide nanoparticles for MR contrast agents. J Mater Chem B, 2017. 5(3): p. 418-422.
164. Mitchell, E., et al., Probing on the hydrothermally synthesized iron oxide nanoparticles for ultra-capacitor applications. Powder Technology, 2015. 272: p. 295-299.
165. Bodtke, A., et al., Horseradish peroxidase (HRP) catalyzed oxidative coupling reactions using aqueous hydrogen peroxide: an environmentally benign procedure for the synthesis of azine pigments. Tetrahedron, 2005. 61(46): p. 10926-10929.
166. Khanmohammadi, M., et al., Horseradish peroxidase-catalyzed hydrogelation for biomedical applications. Biomater Sci, 2018. 6(6): p. 1286-1298.
167. Lee, F., J.E. Chung, and M. Kurisawa, An injectable hyaluronic acid-tyramine hydrogel system for protein delivery. J Control Release, 2009. 134(3): p. 186-93.
168. Darr, A. and A. Calabro, Synthesis and characterization of tyramine-based hyaluronan hydrogels. J Mater Sci Mater Med, 2009. 20(1): p. 33-44.
169. Gutiérrez, M.C., et al., Poly(vinyl alcohol) Scaffolds with Tailored Morphologies for Drug Delivery and Controlled Release. Advanced Functional Materials, 2007. 17(17): p. 3505-3513.
170. Qiao, Y., et al., Preparation of printable double-network hydrogels with rapid self-healing and high elasticity based on hyaluronic acid for controlled drug release. Polymer, 2020. 186.
171. Guvendiren, M., S. Yang, and J.A. Burdick, Swelling-Induced Surface Patterns in Hydrogels with Gradient Crosslinking Density. Advanced Functional Materials, 2009. 19(19): p. 3038-3045.
172. Zhong, X., et al., Fabrication of chitosan/poly(epsilon-caprolactone) composite hydrogels for tissue engineering applications. J Mater Sci Mater Med, 2011. 22(2): p. 279-88.
173. Kakizaki, I., et al., Mechanism for the hydrolysis of hyaluronan oligosaccharides by bovine testicular hyaluronidase. FEBS J, 2010. 277(7): p. 1776-86.
174. Jeon, O., et al., Mechanical properties and degradation behaviors of hyaluronic acid hydrogels cross-linked at various cross-linking densities. Carbohydrate Polymers, 2007. 70(3): p. 251-257.
175. Singh, N., et al., Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev, 2010. 1.
176. Albanese, A., P.S. Tang, and W.C. Chan, The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng, 2012. 14: p. 1-16.
177. Choi, D.H. and H.S.J.A.B.C. Hwang, Anti-inflammation activity of brazilin in TNF-α induced human psoriasis dermatitis skin model. 2019. 62(1): p. 46.
178. Yu, B., Wang, Y.,Huang,S.H. and Yang,J., Interleukin-6 as a Therapeutic Target on Human Cancer. Targeted Cancer Therapy 2016.
179. Waldner, M.J., S. Foersch, and M.F. Neurath, Interleukin-6--a key regulator of colorectal cancer development. Int J Biol Sci, 2012. 8(9): p. 1248-53.
180. Tian, G., et al., Circulating interleukin-6 and cancer: A meta-analysis using Mendelian randomization. Sci Rep, 2015. 5: p. 11394.
181. Rossi, J.F., et al., Interleukin-6 as a therapeutic target. Clin Cancer Res, 2015. 21(6): p. 1248-57.
182. Kumari, N., et al., Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol, 2016. 37(9): p. 11553-11572.
183. Guo, Y., et al., Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev, 2012. 38(7): p. 904-10.
184. Horssen, R.V., Hagen,T.L.M.T. and Eggermont,A.M.M., TNF-α in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility. The Oncologist, 2006. 11: p. 397–408.
185. Costa Brandão Berti, F. and K. Brajão de Oliveira, IL-10 in cancer: Just a classical immunosuppressive factor or also an immunostimulating one? AIMS Allergy and Immunology, 2018. 2(2): p. 88-97.
186. Figueiredo Borgognoni, C., et al., Human macrophage responses to metal-oxide nanoparticles: a review. Artif Cells Nanomed Biotechnol, 2018. 46(sup2): p. 694-703.
187. Lee, S.J., et al., Enhanced anti-tumor immunotherapy by silica-coated magnetic nanoparticles conjugated with ovalbumin. Int J Nanomedicine, 2019. 14: p. 8235-8249.
188. Toda, T. and S. Yoshino, Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles. Int J Immunopathol Pharmacol, 2016. 29(3): p. 408-20.
189. Toyota, H., et al., Vaccination with OVA-bound nanoparticles encapsulating IL-7 inhibits the growth of OVA-expressing E.G7 tumor cells in vivo. Oncol Rep, 2015. 33(1): p. 292-6.
190. Surendran, S.P., et al., Bioactive Nanoparticles for Cancer Immunotherapy. Int J Mol Sci, 2018. 19(12).
191. Darzynkiewicz, Z., et al., Features of apoptotic cells measured by flow cytometry. Cytometry, 1992. 13(8): p. 795-808.
192. Bedner, E., et al., Analysis of apoptosis by laser scanning cytometry. Cytometry, 1999. 35(3): p. 181-95.
193. Da Silva, C.G., et al., Effective chemoimmunotherapy by co-delivery of doxorubicin and immune adjuvants in biodegradable nanoparticles. Theranostics, 2019. 9(22): p. 6485-6500.
194. Zhao, N., et al., Advances in delivery systems for doxorubicin. 2018. 9(5).
195. Cheng, C., et al., Development of a dual drug-loaded hydrogel delivery system for enhanced cancer therapy: in situ formation, degradation and synergistic antitumor efficiency. Journal of Materials Chemistry B, 2017. 5(43): p. 8487-8497.
196. Kim, J., et al., Combination of nitric oxide and drug delivery systems: tools for overcoming drug resistance in chemotherapy. J Control Release, 2017. 263: p. 223-230.
197. Kundur, S., et al., Synergistic anticancer action of quercetin and curcumin against triple-negative breast cancer cell lines. J Cell Physiol, 2019. 234(7): p. 11103-11118.
198. Meng, J., et al., Combination Therapy using Co-encapsulated Resveratrol and Paclitaxel in Liposomes for Drug Resistance Reversal in Breast Cancer Cells in vivo. Sci Rep, 2016. 6: p. 22390.
199. Song, Y.F., et al., Dual subcellular compartment delivery of doxorubicin to overcome drug resistant and enhance antitumor activity. Sci Rep, 2015. 5: p. 16125.
200. Al-Harthi, S.E., et al., Amelioration of doxorubicininduced cardiotoxicity by resveratrol. Mol Med Rep, 2014. 10(3): p. 1455-60.
201. Remesh, A., Toxicities of anticancer drugs and its management. International Journal of Basic & Clinical Pharmacology, 2012. 1(1).
202. Pugazhendhi, A., et al., Toxicity of Doxorubicin (Dox) to different experimental organ systems. Life Sci, 2018. 200: p. 26-30.
203. Zhang, Y., et al., Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer. Sci Rep, 2016. 6: p. 21225.
204. Bolat, Z.B., et al., Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model. Front Bioeng Biotechnol, 2020. 8: p. 50.
205. Kim, T.H., et al., Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta, 2014. 1840(1): p. 615-25.
206. Wen, C., et al., Curcumin reverses doxorubicin resistance via inhibition the efflux function of ABCB4 in doxorubicinresistant breast cancer cells. Mol Med Rep, 2019. 19(6): p. 5162-5168.
207. Rai, G., et al., Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight. Phytomedicine, 2016. 23(3): p. 233-42.
208. Oktem, G., et al., Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis. Exp Toxicol Pathol, 2012. 64(5): p. 471-9.
209. Ko, J.H., et al., The Role of Resveratrol in Cancer Therapy. Int J Mol Sci, 2017. 18(12).
210. Vervandier-Fasseur, D. and N. Latruffe, The Potential Use of Resveratrol for Cancer Prevention. Molecules, 2019. 24(24).
211. Huang, F., et al., Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells. Exp Ther Med, 2014. 7(6): p. 1611-1616.
212. Abedi-Gaballu, F., et al., PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. Appl Mater Today, 2018. 12: p. 177-190.
213. Chauhan, A.S., Dendrimers for Drug Delivery. Molecules, 2018. 23(4).
214. Bastien, E., et al., PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects. Photochem Photobiol Sci, 2015. 14(12): p. 2203-12.
215. Fakhari, A. and J. Anand Subramony, Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J Control Release, 2015. 220(Pt A): p. 465-475.
216. Li, X., et al., In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis. RSC Advances, 2015. 5(123): p. 101494-101506.
217. Mendonca, P.V., et al., Increasing the Bile Acid Sequestration Performance of Cationic Hydrogels by Using an Advanced/Controlled Polymerization Technique. Pharm Res, 2017. 34(9): p. 1934-1943.
218. Stojančević, M., et al., Application of bile acids in drug formulation and delivery. Frontiers in Life Science, 2014. 7(3-4): p. 112-122.
219. Pavlovic, N., et al., Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles. Front Pharmacol, 2018. 9: p. 1283.
220. Cunningham, A.J. and X.X. Zhu, Polymers made of bile acids: from soft to hard biomaterials. Canadian Journal of Chemistry, 2016. 94(8): p. 659-666.
221. Guo, Y., et al., Effects of polymers on the properties of hydrogels constructed using sodium deoxycholate and amino acid. RSC Advances, 2018. 8(16): p. 8699-8708.
222. Zhang, Y., et al., Biodegradable, multiple stimuli-responsive sodium deoxycholate–amino acids–NaCl mixed systems for dye delivery. RSC Adv., 2014. 4(107): p. 62262-62271.
223. Wei, X., et al., Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) copolymers as drug delivery system. Int J Pharm, 2009. 381(1): p. 1-18.
224. Wu, J. and M.J. Sailor, Chitosan Hydrogel-Capped Porous SiO2as a pH Responsive Nano-Valve for Triggered Release of Insulin. Advanced Functional Materials, 2009. 19(5): p. 733-741.
225. Addisu, K.D., et al., Mixed Lanthanide Oxide Nanoparticles Coated with Alginate-Polydopamine as Multifunctional Nanovehicles for Dual Modality: Targeted Imaging and Chemotherapy. ACS Biomaterials Science & Engineering, 2019. 5(10): p. 5453-5469.
226. Hailemeskel, B.Z., et al., Diselenide linkage containing triblock copolymer nanoparticles based on Bi(methoxyl poly(ethylene glycol))-poly(epsilon-carprolactone): Selective intracellular drug delivery in cancer cells. Mater Sci Eng C Mater Biol Appl, 2019. 103: p. 109803.
227. Hanurry, E.Y., et al., Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells. Pharmaceutics, 2020. 12(5).
228. Mekonnen, T.W., et al., Encapsulation of gadolinium ferrite nanoparticle in generation 4.5 poly(amidoamine) dendrimer for cancer theranostics applications using low frequency alternating magnetic field. Colloids Surf B Biointerfaces, 2019. 184: p. 110531.
229. Jiang, L., et al., Entrapping multifunctional dendritic nanoparticles into a hydrogel for local therapeutic delivery and synergetic immunochemotherapy. Nano Research, 2018. 11(11): p. 6062-6073.
230. Hanurry, E.Y., et al., In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers. Mater Sci Eng C Mater Biol Appl, 2019. 106: p. 110245.
231. Darge, H.F., et al., Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy. Int J Pharm, 2019. 572: p. 118799.
232. Shokry, D.S., et al., Formation of a Bile Salt-Drug Hydrogel to Predict Human Intestinal Absorption. J Pharm Sci, 2019. 108(1): p. 279-287.
233. Coello, A., et al., Aggregation behavior of bile salts in aqueous solution. J Pharm Sci, 1996. 85(1): p. 9-15.
234. Sun, X., et al., Rheological properties of the gels of biological surfactant sodium deoxycholate/amino acids/halide salts systems. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014. 457: p. 345-353.
235. Zhang, M., Waldron,K.C.,and Zhu,X.X., Formation of molecular hydrogels from a bile acid derivative and selected carboxylic acids. Rsc Advances, 2016. 6(42): p. 35436-35440.
236. Xu, L., et al., The comparison of rheological properties of aqueous welan gum and xanthan gum solutions. Carbohydr Polym, 2013. 92(1): p. 516-22.
237. Yan, C. and D.J. Pochan, Rheological properties of peptide-based hydrogels for biomedical and other applications. Chem Soc Rev, 2010. 39(9): p. 3528-40.
238. Kaneko, T., et al., Tough, thin hydrogel membranes with giant crystalline domains composed of precisely synthesized macromolecules. Macromolecules, 2005. 38(11): p. 4861-4867.
239. Nurunnabi, M., et al., Design and strategies for bile acid mediated therapy and imaging. RSC Advances, 2016. 6(78): p. 73986-74002.
240. Wang, D. and J. Hao, Self-assembly fibrillar network gels of simple surfactants in organic solvents. Langmuir, 2011. 27(5): p. 1713-7.
241. Yuan, Z., et al., Gel phase originating from molecular quasi-crystallization and nanofiber growth of sodium laurate–water system. Soft Matter, 2008. 4(8).
242. Fan, D.Y., Y. Tian, and Z.J. Liu, Injectable Hydrogels for Localized Cancer Therapy. Front Chem, 2019. 7: p. 675.
243. Li, J. and D.J. Mooney, Designing hydrogels for controlled drug delivery. Nat Rev Mater, 2016. 1(12).
244. Serrano-Aroca, Á., Enhancement of Hydrogels’ Properties for Biomedical Applications: Latest Achievements, in Hydrogels. 2018.
245. Bogdanova, L.R., et al., Micellization in sodium deoxycholate solutions. Colloid Journal, 2012. 74(1): p. 1-6.
246. Chen, J.M., et al., Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by modulating PI3K/Akt signaling pathway. IUBMB Life, 2018. 70(6): p. 491-500.
247. Aluyen, J.K., et al., Resveratrol: potential as anticancer agent. J Diet Suppl, 2012. 9(1): p. 45-56.
248. Motevalli, S.M., et al., Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells. Biophysics Reports, 2019. 5(1): p. 19-30.
249. Taymaz-Nikerel, H., et al., Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells. Sci Rep, 2018. 8(1): p. 13672.
250. Mahbub, A.A., et al., Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. Cell Death Discov, 2015. 1: p. 15043.
251. Stella, G.M., et al., Lung-Seeking Metastases. Cancers (Basel), 2019. 11(7).
252. Zacharias, M., et al., Bulk tumour cell migration in lung carcinomas might be more common than epithelial-mesenchymal transition and be differently regulated. BMC Cancer, 2018. 18(1): p. 717.

全文公開日期 2026/01/12 (校內網路)
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