簡易檢索 / 詳目顯示

研究生: 陳采萱
Tsai-Hsuan Chen
論文名稱: 用簡單的方法製備含微氣泡的靛青綠-紫草素海藻酸鹽載體及其應用
A simple method to prepare indocyanine green-shikonin alginate microbubbles and their application.
指導教授: 白孟宜
Meng-Yi Bai
口試委員: 王毓淇
Yu-Chi Wang
鄭詠馨
Yung-Hsin Cheng
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 醫學工程研究所
Graduate Institute of Biomedical Engineering
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 97
中文關鍵詞: 微氣泡靛青綠海藻膠紫草素電噴灑超音波
外文關鍵詞: microbubbles, indocyanine green, alginate, shikonin, electrospray, ultrasound
相關次數: 點閱:193下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 現今,微氣泡已廣泛被應用在醫學上,無論是顯影劑用於醫學診斷,又或是使微氣泡產生穴蝕效應,作為載體釋放藥物的方式。其相關研究儀器設備、藥物都價值不斐,本研究的目的在於用簡單、低成本的方法製備含微氣泡的靛氰綠-紫草素海藻酸鹽載體,其中靛氰綠是醫學上常用的螢光顯影劑,而紫草素在許多文獻中被指出具有抗癌的效果。本研究採用機械性攪拌方式製備出微氣泡,並利用電噴灑裝置使海藻膠與鈣離子產生共交聯,將疏水性藥物、微氣泡包覆在載體中。本研究採用超音波震盪、往復式震盪恆溫水槽兩種釋放模式,進行體外藥物釋放曲線圖的比較,再對SKOV3、CP70(/A2780)兩株卵巢癌細胞進行細胞毒性測試。針對本研究製備載體之應用,分別拍攝了超音波影像及在紅外光下的螢光影像,結合兩種不同顯影功能的顯影劑。實驗結果發現靛氰綠可以做為界面活性劑增加母液的起泡性,而與往復式震盪恆溫水槽相比,微氣泡透過超音波震盪的方式,可以在固定的時間內釋放出更多藥物。從細胞毒性測試的結果圖中也可以說明紫草素似乎對CP70(/A2780)細胞更有毒性效果。


    Nowadays, microbubbles have been widely used in medical science, such as contrast agent for medical diagnosis, or bursting microbubbles to release the drug from the carrier. As mentioned above, the equipment and drugs for those experiment are expensive. The purpose of this research is to prepare indocyanine green-shikonin alginate microbubbles by a simple and low-cost method. By the way, indocyanine green is a commonly fluorescent agent in medicine, and shikonin has demonstrated potent anti-cancer activities. In this study, microbubbles were produced by stirring in a high speed. The calcium ions in the solution cross-linked alginate during the electrospray, then the hydrophobic drug and microbubbles would be encapsulated in the carrier. The study was compared the curve of drug release in two models, which one was in ultrasonic cleaner, and the other one was in reciprocal shaking water baths. In order to prove the cytotoxicity of ovarian cancer cells, we chose SKOV3 and CP70 (/A2780) cells to do the test. Then, ultrasonic images and fluorescent images were taken respectively as their applications. The experimental results were found that indocyanine green has amphiphilic properties in chemical structure, so it’s a surfactant to increase the foaming property of solution. In a fixed time, More drug is released by ultrasonication. The result of MTT assay seems that shikonin is more toxic on CP70(/A2780) cells.

    中文摘要 I ABSTRACT II 誌謝 III 第一章、緒論 2 1.1 前言 2 1.2 實驗動機與目的 2 1.3 實驗設計 3 第二章、文獻回顧 4 2.1 卵巢癌 4 2.2 微氣泡 5 2.2.1 原理 5 2.2.2 應用 6 2.3 電噴灑 7 2.4 靛氰綠-海藻酸鹽(ICG-ALG) 8 2.5 紫草素-海藻酸鹽(SK-ALG) 9 第三章、材料與方法 10 3.1 藥品 10 3.2 材料 11 3.3 軟體 11 3.4 儀器 12 3.5 實驗步驟 13 3.5.1 母液製備 14 3.5.2 發泡溶液製備 14 3.5.3 電噴灑(Electrospray) 15 3.5.4 細胞培養基本操作 15 3.5.5 細胞毒性測試 20 3.5.6 藥物釋放測試 21 3.5.7 超音波影像拍攝前處理-製備仿體 22 3.5.8 掃描式電子顯微鏡影像拍攝前處理 23 第四章、實驗結果與討論 24 4.1 載體表面型態鑑定 24 4.1.1 光學顯微鏡 24 4.1.2 掃描式電子顯微鏡 31 4.2 吸收光譜圖 31 4.3 超音波影像之結果分析 32 4.4 MMBs在紅外光下顯影之結果 33 4.5 載體藥物釋放之結果 34 4.6 MMBs對細胞之毒性測試 35 4.6.1 CP70(/A2780) 35 4.6.2 SKOV-3 36 第五章、結論 37 第六章、未來展望 38 第七章、參考文獻 39

    [1] K. Delmar, H. Bianco-Peled, Composite chitosan hydrogels for extended release of hydrophobic drugs, Carbohydrate polymers 136 (2016) 570-580.
    [2] C.-P.J. Wang, M.J. Byun, S.-N. Kim, W. Park, H.H. Park, T.-H. Kim, J.S. Lee, C.G. Park, Biomaterials as therapeutic drug carriers for inflammatory bowel disease treatment, Journal of Controlled Release (2022).
    [3] A. George, P.A. Shah, P.S. Shrivastav, Natural biodegradable polymers based nano-formulations for drug delivery: A review, International journal of pharmaceutics 561 (2019) 244-264.
    [4] C. Gutierrez Cisneros, V. Bloemen, A. Mignon, Synthetic, natural, and semisynthetic polymer carriers for controlled nitric oxide release in dermal applications: a review, Polymers 13(5) (2021) 760.
    [5] G.E. Cacciamani, A. Shakir, A. Tafuri, K. Gill, J. Han, N. Ahmadi, P. Hueber, M. Gallucci, G. Simone, R. Campi, Best practices in near-infrared fluorescence imaging with indocyanine green (NIRF/ICG)-guided robotic urologic surgery: a systematic review-based expert consensus, World Journal of Urology 38(4) (2020) 883-896.
    [6] R.A. Pathak, A.K. Hemal, Intraoperative ICG-fluorescence imaging for robotic-assisted urologic surgery: current status and review of literature, International Urology and Nephrology 51(5) (2019) 765-771.
    [7] T. Yanagita, M. Hara, S. Osaga, N. Nakai, Y. Maeda, K. Shiga, T. Hirokawa, Y. Matsuo, H. Takahashi, S. Takiguchi, Efficacy of intraoperative ICG fluorescence imaging evaluation for preventing anastomotic leakage after left-sided colon or rectal cancer surgery: a propensity score-matched analysis, Surgical Endoscopy 35(5) (2021) 2373-2385.
    [8] J. Pan, H. Deng, S. Hu, C. Xia, Y. Chen, J. Wang, Y. Wang, Real-time surveillance of surgical margins via ICG-based near-infrared fluorescence imaging in patients with OSCC, World journal of surgical oncology 18(1) (2020) 1-8.
    [9] G.L. Baiocchi, G. Guercioni, N. Vettoretto, S. Scabini, P. Millo, A. Muratore, M. Clementi, G. Sica, P. Delrio, G. Longo, ICG fluorescence imaging in colorectal surgery: a snapshot from the ICRAL study group, BMC surgery 21(1) (2021) 1-7.
    [10] R. Blanco-Colino, E. Espin-Basany, Intraoperative use of ICG fluorescence imaging to reduce the risk of anastomotic leakage in colorectal surgery: a systematic review and meta-analysis, Techniques in coloproctology 22(1) (2018) 15-23.
    [11] J. Wischhusen, F. Padilla, Ultrasound-targeted microbubble destruction (UTMD) for localized drug delivery into tumor tissue, Irbm 40(1) (2019) 10-15.
    [12] S.M. Chowdhury, L. Abou-Elkacem, T. Lee, J. Dahl, A.M. Lutz, Ultrasound and microbubble mediated therapeutic delivery: Underlying mechanisms and future outlook, Journal of Controlled Release 326 (2020) 75-90.
    [13] A.-H. Liao, C.-H. Wang, P.-Y. Weng, Y.-C. Lin, H. Wang, H.-K. Chen, H.-L. Liu, H.-C. Chuang, C.-P. Shih, Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery, JCI insight 5(3) (2020).
    [14] K. Kooiman, S. Roovers, S.A. Langeveld, R.T. Kleven, H. Dewitte, M.A. O'Reilly, J.-M. Escoffre, A. Bouakaz, M.D. Verweij, K. Hynynen, Ultrasound-responsive cavitation nuclei for therapy and drug delivery, Ultrasound in Medicine & Biology 46(6) (2020) 1296-1325.
    [15] Y.-J. Ho, H.-C. Chang, C.-W. Lin, C.-H. Fan, Y.-C. Lin, K.-C. Wei, C.-K. Yeh, Oscillatory behavior of microbubbles impacts efficacy of cellular drug delivery, Journal of Controlled Release 333 (2021) 316-327.
    [16] H. Li, Y. Zhang, H. Shu, W. Lv, C. Su, F. Nie, Highlights in ultrasound-targeted microbubble destruction-mediated gene/drug delivery strategy for treatment of malignancies, International Journal of Pharmaceutics (2021) 121412.
    [17] Y.-J. Ho, C.-C. Huang, C.-H. Fan, H.-L. Liu, C.-K. Yeh, Ultrasonic technologies in imaging and drug delivery, Cellular and Molecular Life Sciences 78(17) (2021) 6119-6141.
    [18] J. He, Z. Liu, X. Zhu, H. Xia, H. Gao, J. Lu, Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy, Pharmaceutics 14(8) (2022) 1642.
    [19] L. Wang, B. Zhu, J. Huang, X. Xiang, Y. Tang, L. Ma, F. Yan, C. Cheng, L. Qiu, Ultrasound-targeted microbubble destruction augmented synergistic therapy of rheumatoid arthritis via targeted liposomes, Journal of Materials Chemistry B 8(24) (2020) 5245-5256.
    [20] S. Wang, X. Guo, W. Xiu, Y. Liu, L. Ren, H. Xiao, F. Yang, Y. Gao, C. Xu, L. Wang, Accelerating thrombolysis using a precision and clot-penetrating drug delivery strategy by nanoparticle-shelled microbubbles, Science advances 6(31) (2020) eaaz8204.
    [21] S.-K. Wu, C.-L. Tsai, Y. Huang, K. Hynynen, Focused ultrasound and microbubbles-mediated drug delivery to brain tumor, Pharmaceutics 13(1) (2020) 15.
    [22] L. Meng, X. Liu, Y. Wang, W. Zhang, W. Zhou, F. Cai, F. Li, J. Wu, L. Xu, L. Niu, Sonoporation of cells by a parallel stable cavitation microbubble array, Advanced Science 6(17) (2019) 1900557.
    [23] E. Stride, C. Coussios, Nucleation, mapping and control of cavitation for drug delivery, Nature Reviews Physics 1(8) (2019) 495-509.
    [24] I.J. Chung, H. Moon, S.I. Jeon, H.J. Lee, C.-H. Ahn, Ultrasound-triggered imaging and drug delivery using microbubble-self-aggregate complexes, Journal of Biomaterials Science, Polymer Edition 33(1) (2022) 57-76.
    [25] L. Zhang, L. Sun, Q. Tang, S. Sun, L. Zeng, J. Ma, X. Li, H. Ge, X. Liang, Cascade Drug Delivery through Tumor Barriers of Pancreatic Cancer via Ultrasound in Combination with Functional Microbubbles, ACS Biomaterials Science & Engineering 8(4) (2022) 1583-1595.
    [26] H. Xia, D. Yang, W. He, X. Zhu, Y. Yan, Z. Liu, T. Liu, J. Yang, S. Tan, J. Jiang, Ultrasound-mediated microbubbles cavitation enhanced chemotherapy of advanced prostate cancer by increasing the permeability of blood-prostate barrier, Translational oncology 14(10) (2021) 101177.
    [27] A.-H. Liao, Y.-C. Chen, C.-Y. Chen, S.-C. Chang, H.-C. Chuang, D.-L. Lin, C.-P. Chiang, C.-H. Wang, J.-K. Wang, Mechanisms of ultrasound-microbubble cavitation for inducing the permeability of human skin, Journal of Controlled Release 349 (2022) 388-400.
    [28] S.C. Moorcroft, D.G. Jayne, S.D. Evans, Z.Y. Ong, Stimuli‐responsive release of antimicrobials using hybrid inorganic nanoparticle‐associated drug‐delivery systems, Macromolecular bioscience 18(12) (2018) 1800207.
    [29] B. Joshi, A. Joshi, Ultrasound-based drug delivery systems, Bioelectronics and Medical Devices (2019) 241-260.
    [30] R. Sanwal, K. Joshi, M. Ditmans, S.S. Tsai, W.L. Lee, Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities, Biomedicines 9(7) (2021) 803.
    [31] S. Snipstad, K. Vikedal, M. Maardalen, A. Kurbatskaya, E. Sulheim, C. de Lange Davies, Ultrasound and microbubbles to beat barriers in tumors: Improving delivery of nanomedicine, Advanced Drug Delivery Reviews 177 (2021) 113847.
    [32] Z. Izadifar, P. Babyn, D. Chapman, Ultrasound cavitation/microbubble detection and medical applications, Journal of Medical and Biological Engineering 39(3) (2019) 259-276.
    [33] A.-H. Liao, K.-H. Lin, H.-C. Chuang, C.-H. Tsai, Y.-C. Lin, C.-H. Wang, C.-P. Shih, H.-L. Liu, Low-frequency dual-frequency ultrasound-mediated microbubble cavitation for transdermal minoxidil delivery and hair growth enhancement, Scientific Reports 10(1) (2020) 1-12.
    [34] Y. Gong, D. Ye, C.-Y. Chien, Y. Yue, H. Chen, Comparison of sonication patterns and microbubble administration strategies for focused ultrasound-mediated large-volume drug delivery, IEEE Transactions on Biomedical Engineering (2022).
    [35] A. Presset, C. Bonneau, S. Kazuyoshi, L. Nadal-Desbarats, T. Mitsuyoshi, A. Bouakaz, N. Kudo, J.-M. Escoffre, N. Sasaki, Endothelial cells, first target of drug delivery using microbubble-assisted ultrasound, Ultrasound in Medicine & Biology 46(7) (2020) 1565-1583.
    [36] S. Snipstad, E. Sulheim, C. de Lange Davies, C. Moonen, G. Storm, F. Kiessling, R. Schmid, T. Lammers, Sonopermeation to improve drug delivery to tumors: from fundamental understanding to clinical translation, Expert opinion on drug delivery 15(12) (2018) 1249-1261.
    [37] J. He, Z. Liu, X. Zhu, H. Xia, H. Gao, J. Lu, Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy. Pharmaceutics 2022, 14, 1642, (2022).
    [38] Y. Peng, C. Peng, T. Nguyen, T. Sun, T. Porter, N. McDannold, J.N. Kheir, B.D. Polizzotti, Engineering caged microbubbles for controlled acoustic cavitation and pressure sensing, ACS Materials Letters 3(7) (2021) 978-987.
    [39] T. Di Ianni, R.J. Bose, U.K. Sukumar, S. Bachawal, H. Wang, A. Telichko, C. Herickhoff, E. Robinson, S. Baker, J.G. Vilches-Moure, Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs, Journal of Controlled Release 309 (2019) 1-10.
    [40] J.H. Lee, H. Moon, H. Han, I.J. Lee, D. Kim, H.J. Lee, S.-W. Ha, H. Kim, J.W. Chung, Antitumor effects of intra-arterial delivery of albumin-doxorubicin nanoparticle conjugated microbubbles combined with ultrasound-targeted microbubble activation on VX2 rabbit liver tumors, Cancers 11(4) (2019) 581.
    [41] K.-H. Song, B.K. Harvey, M.A. Borden, State-of-the-art of microbubble-assisted blood-brain barrier disruption, Theranostics 8(16) (2018) 4393.
    [42] R.J. Morgan Jr, R.D. Alvarez, D.K. Armstrong, B. Boston, L.-m. Chen, L. Copeland, J. Fowler, D.K. Gaffney, D. Gershenson, B.E. Greer, Ovarian cancer. Clinical practice guidelines in oncology, Journal of the National Comprehensive Cancer Network: JNCCN 6(8) (2008) 766-794.
    [43] J.M. Hansen, R.L. Coleman, A.K. Sood, Targeting the tumour microenvironment in ovarian cancer, European Journal of Cancer 56 (2016) 131-143.
    [44] R. Pokhriyal, R. Hariprasad, L. Kumar, G. Hariprasad, Chemotherapy resistance in advanced ovarian cancer patients, Biomarkers in cancer 11 (2019) 1179299X19860815.
    [45] E.-I. Matthaiou, J. Barar, R. Sandaltzopoulos, C. Li, G. Coukos, Y. Omidi, Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer, International journal of nanomedicine 9 (2014) 1855.
    [46] Z. Wang, J. Yin, M. Li, J. Shen, Z. Xiao, Y. Zhao, C. Huang, H. Zhang, Z. Zhang, C.H. Cho, Combination of shikonin with paclitaxel overcomes multidrug resistance in human ovarian carcinoma cells in a P-gp-independent manner through enhanced ROS generation, Chinese medicine 14(1) (2019) 1-11.
    [47] K.H. Lee, H. Kim, J.W. KuK, J.D. Chung, S. Park, E.E. Kwon, Micro-bubble flow simulation of dissolved air flotation process for water treatment using computational fluid dynamics technique, Environmental Pollution 256 (2020) 112050.
    [48] A. Kawahara, M. Sadatomi, F. Matsuyama, H. Matsuura, M. Tominaga, M. Noguchi, Prediction of micro-bubble dissolution characteristics in water and seawater, Experimental Thermal and Fluid Science 33(5) (2009) 883-894.
    [49] M. Sumikura, M. Hidaka, H. Murakami, Y. Nobutomo, T. Murakami, Ozone micro-bubble disinfection method for wastewater reuse system, Water Science and Technology 56(5) (2007) 53-61.
    [50] S. Ihara, T. Hirohata, Y. Kominato, C. Yamabe, H. Ike, K. Hakiai, K. Hirabayashi, M. Tamagawa, Water treatment using discharge generated in cavitation field with micro bubble cloud, Electrical Engineering in Japan 186(4) (2014) 1-10.
    [51] M.J. Blomley, J.C. Cooke, E.C. Unger, M.J. Monaghan, D.O. Cosgrove, Microbubble contrast agents: a new era in ultrasound, Bmj 322(7296) (2001) 1222-1225.
    [52] P.A. Dayton, J.J. Rychak, Molecular ultrasound imaging using microbubble contrast agents, Frontiers in Bioscience-Landmark 12(13) (2007) 5124-5142.
    [53] R.P. Kedar, D. Cosgrove, V.R. McCready, J.C. Bamber, E.R. Carter, Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress, Radiology 198(3) (1996) 679-686.
    [54] K. Ferrara, R. Pollard, M. Borden, Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery, Annual review of biomedical engineering 9(1) (2007) 415-447.
    [55] J.-M. Correas, M. Claudon, F. Tranquart, O. Hélénon, The kidney: imaging with microbubble contrast agents, Ultrasound quarterly 22(1) (2006) 53-66.
    [56] E. Quaia, F. Calliada, M. Bertolotto, S. Rossi, L. Garioni, L. Rosa, R. Pozzi-Mucelli, Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride–filled microbubble contrast agent: diagnostic performance and confidence, Radiology 232(2) (2004) 420-430.
    [57] D.H. Simpson, C.T. Chin, P.N. Burns, Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents, IEEE transactions on ultrasonics, ferroelectrics, and frequency control 46(2) (1999) 372-382.
    [58] S.H. Bloch, M. Wan, P.A. Dayton, K.W. Ferrara, Optical observation of lipid-and polymer-shelled ultrasound microbubble contrast agents, Applied physics letters 84(4) (2004) 631-633.
    [59] C.F. Caskey, S.M. Stieger, S. Qin, P.A. Dayton, K.W. Ferrara, Direct observations of ultrasound microbubble contrast agent interaction with the microvessel wall, The Journal of the Acoustical Society of America 122(2) (2007) 1191-1200.
    [60] G. Xie, L. Zhang, J. Pan, X. Zhang, S.-K. Sun, Green and Kilogram-Scale Synthesis of Fe Hydrogel for Photothermal Therapy of Tumors in Vivo, ACS Biomaterials Science & Engineering 6(7) (2020) 4276-4284.
    [61] L. Huang, J. Zhou, Y. Chen, W. Li, X. Han, L. Wang, Engineering microcapsules for simultaneous delivery of combinational therapeutics, Advanced Materials Technologies 5(11) (2020) 2000623.
    [62] R. Sun, H. Chen, L. Sutrisno, N. Kawazoe, G. Chen, Nanomaterials and their composite scaffolds for photothermal therapy and tissue engineering applications, Science and Technology of Advanced Materials 22(1) (2021) 404-428.
    [63] X. Su, Y. Cao, Y. Liu, B. Ouyang, B. Ning, Y. Wang, H. Guo, Z. Pang, S. Shen, Localized disruption of redox homeostasis boosting ferroptosis of tumor by hydrogel delivery system, Materials Today Bio 12 (2021) 100154.
    [64] Y. Cao, Q. Ren, R. Hao, Z. Sun, Innovative strategies to boost photothermal therapy at mild temperature mediated by functional nanomaterials, Materials & Design (2022) 110391.
    [65] H. Pan, C. Zhang, T. Wang, J. Chen, S.-K. Sun, In situ fabrication of intelligent photothermal indocyanine green–alginate hydrogel for localized tumor ablation, ACS applied materials & interfaces 11(3) (2018) 2782-2789.
    [66] S. Zhang, Q. Gao, W. Li, L. Zhu, Q. Shang, S. Feng, J. Jia, Q. Jia, S. Shen, Z. Su, Shikonin inhibits cancer cell cycling by targeting Cdc25s, BMC cancer 19(1) (2019) 1-9.
    [67] W. Li, J. Liu, Y. Zhao, PKM2 inhibitor shikonin suppresses TPA‐induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells, Molecular carcinogenesis 53(5) (2014) 403-412.
    [68] Y. Wang, F. Hao, Y. Nan, L. Qu, W. Na, C. Jia, X. Chen, PKM2 inhibitor shikonin overcomes the cisplatin resistance in bladder cancer by inducing necroptosis, International journal of biological sciences 14(13) (2018) 1883.
    [69] U. Thonsri, W. Seubwai, S. Waraasawapati, S. Wongkham, T. Boonmars, U. Cha'on, C. Wongkham, Antitumor effect of Shikonin, a PKM2 inhibitor, in cholangiocarcinoma cell lines, Anticancer Research 40(9) (2020) 5115-5124.
    [70] T. Liu, S. Li, L. Wu, Q. Yu, J. Li, J. Feng, J. Zhang, J. Chen, Y. Zhou, J. Ji, Experimental study of hepatocellular carcinoma treatment by shikonin through regulating PKM2, Journal of hepatocellular carcinoma 7 (2020) 19.
    [71] W. Li, J. Liu, K. Jackson, R. Shi, Y. Zhao, Sensitizing the therapeutic efficacy of taxol with shikonin in human breast cancer cells, PloS one 9(4) (2014) e94079.
    [72] B. Liu, J. Jin, Z. Zhang, L. Zuo, M. Jiang, C. Xie, Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2–AMPK–PGC1α signaling pathway, Biochemistry and Cell Biology 97(4) (2019) 397-405.
    [73] W. Yang, J. Liu, L. Hou, Q. Chen, Y. Liu, Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line, Life Sciences 265 (2021) 118796.
    [74] J. Chen, J. Xie, Z. Jiang, B. Wang, Y. Wang, X. Hu, Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2, Oncogene 30(42) (2011) 4297-4306.
    [75] J. Li, J. Pang, Z. Liu, X. Ge, Y. Zhen, C.C. Jiang, Y. Liu, Q. Huo, Y. Sun, H. Liu, Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways, Scientific reports 11(1) (2021) 1-13.
    [76] Q. Zhang, Q. Liu, S. Zheng, T. Liu, L. Yang, X. Han, X. Lu, Shikonin inhibits tumor growth of ESCC by suppressing PKM2 mediated aerobic glycolysis and STAT3 phosphorylation, Journal of Cancer 12(16) (2021) 4830.
    [77] W. Li, C. Zhang, A. Ren, T. Li, R. Jin, G. Li, X. Gu, R. Shi, Y. Zhao, Shikonin suppresses skin carcinogenesis via inhibiting cell proliferation, PLoS One 10(5) (2015) e0126459.
    [78] J.-c. Tang, Y.-G. Ren, J. Zhao, F. Long, J.-y. Chen, Z. Jiang, Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway, Life sciences 204 (2018) 71-77.
    [79] H. Wu, J. Xie, Q. Pan, B. Wang, D. Hu, X. Hu, Anticancer agent shikonin is an incompetent inducer of cancer drug resistance, PloS one 8(1) (2013) e52706.
    [80] Y. Liu, T. Li, Y. Han, F. Li, Y. Liu, Recent development of electrospun wound dressing, Current Opinion in Biomedical Engineering 17 (2021) 100247.
    [81] H. Jose, K. Krishnakumar, B. Dineshkumar, Herbal extracts based scaffolds for wound healing therapy, Research Journal of Pharmacy and Technology 14(3) (2021) 1805-1810.
    [82] J. Wróblewska-Krepsztul, T. Rydzkowski, I. Michalska-Pożoga, V.K. Thakur, Biopolymers for biomedical and pharmaceutical applications: recent advances and overview of alginate electrospinning, Nanomaterials 9(3) (2019) 404.
    [83] 賴俊延, 超音波穴蝕效應於基因傳遞效率之研究, (2005).
    [84] M. Earle, G. De Portu, E. DeVos, Agar ultrasound phantoms for low-cost training without refrigeration, African Journal of Emergency Medicine 6(1) (2016) 18-23.
    [85] N. Maikusa, T. Fukami, T. Yuasa, Y. Tamura, T. Akatsuka, Fundamental study on subharmonic imaging by irradiation of amplitude-modulated ultrasound waves, The Journal of the Acoustical Society of America 122(1) (2007) 672-676.
    [86] N. Maikusa, T. Fukami, T. Yuasa, Y. Tamura, T. Akatsuka, P2B-2 Fundamental Study of Subharmonic Imaging Used Amplitude-Modulated Ultrasound Wave, 2006 IEEE Ultrasonics Symposium, IEEE, 2006, pp. 1576-1579.
    [87] M. Zambacevičienė, R. Jurkonis, S. Gelman, A. Sakalauskas, RF ultrasound based estimation of pulsatile flow induced microdisplacements in phantom, World Congress on Medical Physics and Biomedical Engineering 2018, Springer, 2019, pp. 601-605.
    [88] W. Wang, J. Du, W. Wang, Improved MUSIC method for spatial spectrum estimation of ultrasound sources, 2017 IEEE 7th Annual International Conference on CYBER Technology in Automation, Control, and Intelligent Systems (CYBER), IEEE, 2017, pp. 898-902.
    [89] S. de Préval Eugénie, D. Fabrice, C. Gérard, M. Samir, Effect of bulk viscosity and surface tension kinetics on structure of foam generated at the pilot scale, Food Hydrocolloids 34 (2014) 104-111.
    [90] H. Ikagawa, M. Yoneda, M. Iwaki, Z. Isogai, K. Tsujii, R. Yamazaki, T. Kamiya, M. Zako, Chemical toxicity of indocyanine green damages retinal pigment epithelium, Investigative ophthalmology & visual science 46(7) (2005) 2531-2539.
    [91] B. Niu, P. Shao, Y. Luo, P. Sun, Recent advances of electrosprayed particles as encapsulation systems of bioactives for food application, Food Hydrocolloids 99 (2020) 105376.
    [92] Y. Gan, H. Li, Z. Jiang, X. Chen, Y. Luo, Y. Tong, Y. Shi, X. Jiang, An experimental investigation on the electrospray characteristics in a meso-scale system at different modes, Experimental Thermal and Fluid Science 106 (2019) 130-137.
    [93] H. Alkhatib, E. Assadpour, A.S.M. Sabere, F. Mohamed, S.M. Jafari, Optimizing the encapsulation of black seed oil into alginate beads by ionic gelation, Journal of Food Engineering 328 (2022) 111065.
    [94] A.Í. Morais, E.G. Vieira, S. Afewerki, R.B. Sousa, L.M. Honorio, A.N. Cambrussi, J.A. Santos, R.D. Bezerra, J.A. Furtini, E.C. Silva-Filho, Fabrication of polymeric microparticles by electrospray: the impact of experimental parameters, Journal of functional biomaterials 11(1) (2020) 4.
    [95] H. Lee, S. An, S. Kim, B. Jeon, M. Kim, I.S. Kim, Readily functionalizable and stabilizable polymeric particles with controlled size and morphology by electrospray, Scientific reports 8(1) (2018) 1-10.
    [96] Z.-C. Yao, C. Zhang, Z. Ahmad, Y. Peng, M.-W. Chang, Microparticle formation via tri-needle coaxial electrospray at stable jetting modes, Industrial & Engineering Chemistry Research 59(32) (2020) 14423-14432.
    [97] M. Abedi Ostad, R. Arezuman, F. Oroojalian, A. Hanafi, A. Amani, Introducing humidity and temperature as important parameters determining the size of chitosan nanoparticles prepared by electrospray, Nanomedicine Research Journal 6(4) (2021) 385-395.
    [98] E. Barbero-Colmenar, M. Guastaferro, L. Baldino, S. Cardea, E. Reverchon, Supercritical CO2 Assisted Electrospray to Produce Poly (lactic-co-glycolic Acid) Nanoparticles, ChemEngineering 6(5) (2022) 66.
    [99] A. Valipouri, H. Hosseinian, S.A.H. Ravandi, A. Karimian, Development and optimization of the novel scale-up fabrication method of polyvinylpyrrolidone (PVP) microparticles, Journal of Electrostatics 118 (2022) 103725.
    [100] H. Zhou, P. Biswas, The prediction of size and charge of particles formed from evaporation of charged droplets generated in an electrospray system, Chemical Engineering Science 231 (2021) 116237.
    [101] M.E.H. El Nokab, A. Lasorsa, K.O. Sebakhy, F. Picchioni, P.C. van der Wel, Solid-state NMR spectroscopy insights for resolving different water pools in alginate hydrogels, Food Hydrocolloids 127 (2022) 107500.
    [102] 汤桂平, 严倩, 刘洁, 宋波, 文世峰, 史玉升, 3D 打印琼脂糖和海藻酸钠复合水凝胶组织与性能研究, 材料工程 49(5) (2021) 66-74.
    [103] K. Hudnall, Cross-linking of Polymannuronate During Spray-drying to Form Microcapsules, University of California, Davis, 2019.
    [104] E.D. Cosco, I. Lim, E.M. Sletten, Photophysical properties of indocyanine green in the shortwave infrared region, ChemPhotoChem 5(8) (2021) 727-734.
    [105] K. Gowsalya, V. Yasothamani, R. Vivek, Emerging indocyanine green-integrated nanocarriers for multimodal cancer therapy: a review, Nanoscale Advances 3(12) (2021) 3332-3352.
    [106] 冯伟, 马建文, 饶梅冬, 紫草素诱导卵巢癌 SKOV3 和 A2780 细胞坏死性凋亡的作用及其机制研究, 中国药业 28(1) (2019) 19-23.
    [107] 王汝兴, 鲁艳杰, 周健, 许倩, 紫草素对人卵巢癌细胞 SKOV3 细胞增殖和凋亡的影响, 中药药理与临床 32(2) (2016) 76-79.
    [108] S. Mindt, I. Karampinis, M. John, M. Neumaier, K. Nowak, Stability and degradation of indocyanine green in plasma, aqueous solution and whole blood, Photochemical & Photobiological Sciences 17(9) (2018) 1189-1196.
    [109] C. Shirata, J. Kaneko, Y. Inagaki, T. Kokudo, M. Sato, S. Kiritani, N. Akamatsu, J. Arita, Y. Sakamoto, K. Hasegawa, Near-infrared photothermal/photodynamic therapy with indocyanine green induces apoptosis of hepatocellular carcinoma cells through oxidative stress, Scientific reports 7(1) (2017) 1-8.

    無法下載圖示 全文公開日期 2032/09/30 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)
    全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
    QR CODE