本研究成功合成出MnOx@BSA-IR780-GOx (MBIG)多功能奈米複合材料，MnOx可以由類芬頓反應(Fenten-likereaction)生成不同價數之錳離子。此外小牛血清蛋白(BSA)具有良好的穩定性與生物相容性，所以用此將MnOx給包覆住。而且BSA表面含有豐富的官能基可以做後續的發展，因此將具有光熱與光動力功能的IR780及酵素反應的葡萄糖氧化酶(GOx)結合於材料上，前者是經由雷射照射後可以藉由產生的高溫及活性氧物質(ROS)來破壞癌細胞，而後者是利用酵素催化來增進治療的功效。
材料鑑定方面利用TEM、FTIR、DLS、UV-vis、MRI等儀器來分析奈米材料結構、組成與顯影性質。在檢驗化學動力治療上，配置不同的pH值環境測試，驗證酸性環境下夠有效進行類芬頓反應。且利用單一雷射(808 nm)激發材料能產生單態氧(1O2)展現出其光動力的功效；此外材料也具有良好的光熱穩定性且光熱轉化效率(33.8%)。在催化的能力上，透過測量H2O2、葡萄糖酸及溶氧量等，確認其氧化酶之活性。並且模擬微腫瘤環境(pH=5.5、過量H2O2)促使材料產生O2與Mn2+，此進一步可克服缺氧的限制及應用於MRI顯影，顯著提升治療的功效。
於生物應用上，首先材料藉由細胞毒性確認其絕佳的安全性。接著對癌細胞進行多重治療，證實在細胞內能有效產生ROS與O2，細胞存活率最終僅剩約10%，達到出色的效果。最後對細胞攝取進行探討，得知材料主要是藉由小窩蛋白介導進入細胞，且適當的溫度與能量有助於材料被細胞攝取。

In this study, a multifunctional nanocomposite was successfully developed at room temperature using bovine serum albumin (BSA) as carrier to integrate Fenton-like metal (MnOx), photothermal agents (IR780), and glucose oxidase (GOx) in one platform. MnOx and IR780 dye were strongly chelated through self-assembly process due to the presence of different functional groups on the surface of BSA. Furthermore, crosslinking chemistry (EDC/NHS-sulfo) between BSA and GOx was developed in order to construct MnOx@BSA-IR780-GOx (MBIG) nanocomposites.
The nanocomposites exhibited excellent biocompatibility due to the presence of BSA, a biocompatible molecule. The optical and surface characterizations of the as-prepared multifunctional MBIG nanocomposites were carried out using TEM, FTIR, DLS, and optical spectroscopy. MBIG efficiently produced singlet oxygen (1O2) for chemodynamic therapy (CDT) in cidic conditions. Interestingly, Mn2+ ion triggers depletion of intercellular glutathione (GSH) level resulting enhanced CDT effects. Upon 808 nm laser irradiations, MBIG generate harmful reactive oxygen species (ROS) and high thermal conversion efficiency (Ƞ=33.8%). The contrasting effects of Mn2+ showing superior T2-dominating effect for anticancer diagnosis. Additionally, glucose, an intercellular nutrient, were effectively decomposed to gluconic acid and H2O2 by the catalytic activity of GOx, causing starvation and oxidation therapy for anticancer treatment. The experimental evidence was confirmed using in vitro cellular investigation, in which the nanocomposite possessed excellent biocompatibility towards various cancer cells. Furthermore, the imaging analysis verified that the nanocomposite produced a red emitting confocal picture using cancer cells, and the cellular uptake process was studied using caveolin-mediated endocytosis routes that were temperature and energy dependent. Overall, the as-prepared nanocomposite demonstrated excellent therapeutic effectiveness in the presence of laser irradiation, H2O2, and glucose substrate through PDT, CDT, PTT, and enzyme reaction. The current MBIG nanocomposite findings might be regarded as a promising therapeutic agent in future nanomedicine.

[1] Rockenberger, J. A new non-hydrolic single-precursor approach to surfactant-capped nanocrystals of transition metal oxides. 1999.
[2] Na, H. B.; Lee, J. H.; An, K.; Park, Y. I.; Park, M.; Lee, I. S.; Nam, D. H.; Kim, S. T.; Kim, S. H.; Kim, S. W. Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. Angewandte Chemie 2007, 119 (28), 5493-5497.
[3] Ji, T.; Zhao, Y.; Ding, Y.; Nie, G. Using functional nanomaterials to target and regulate the tumor microenvironment: diagnostic and therapeutic applications. Advanced Materials 2013, 25 (26), 3508-3525.
[4] Zhang, H.; Zeng, W.; Pan, C.; Feng, L.; Ou, M.; Zeng, X.; Liang, X.; Wu, M.; Ji, X.; Mei, L. SnTe@ MnO2‐SP nanosheet–based intelligent nanoplatform for second near‐infrared light–mediated cancer theranostics. Advanced Functional Materials 2019, 29 (37), 1903791.
[5] Liang, R.; Liu, L.; He, H.; Chen, Z.; Han, Z.; Luo, Z.; Wu, Z.; Zheng, M.; Ma, Y.; Cai, L. Oxygen-boosted immunogenic photodynamic therapy with gold nanocages@ manganese dioxide to inhibit tumor growth and metastases. Biomaterials 2018, 177, 149-160.
[6] Tang, W.; Fan, W.; Zhang, W.; Yang, Z.; Li, L.; Wang, Z.; Chiang, Y. L.; Liu, Y.; Deng, L.; He, L. Wet/sono‐chemical synthesis of enzymatic two‐dimensional MnO2 nanosheets for synergistic catalysis‐enhanced phototheranostics. Advanced Materials 2019, 31 (19), 1900401.
[7] Yang, G.; Xu, L.; Chao, Y.; Xu, J.; Sun, X.; Wu, Y.; Peng, R.; Liu, Z. Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nature communications 2017, 8 (1), 1-13.
[8] Ding, B.; Zheng, P.; Ma, P.; Lin, J. Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications. Adv Mater 2020, 32 (10), e1905823. DOI: 10.1002/adma.201905823 From NLM PubMed-not-MEDLINE.
[9] Lu, Y.; Zhang, L.; Li, J.; Su, Y. D.; Liu, Y.; Xu, Y. J.; Dong, L.; Gao, H. L.; Lin, J.; Man, N. MnO nanocrystals: a platform for integration of MRI and genuine autophagy induction for chemotherapy. Advanced Functional Materials 2013, 23 (12), 1534-1546.
[10] Zhu, H.; Fan, J.; Wang, B.; Peng, X. Fluorescent, MRI, and colorimetric chemical sensors for the first-row d-block metal ions. Chemical Society Reviews 2015, 44 (13), 4337-4366.
[11] Estelrich, J.; Sánchez-Martín, M. J.; Busquets, M. A. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents. International journal of nanomedicine 2015, 10, 1727.
[12] García-Hevia, L.; Bañobre-López, M.; Gallo, J. Recent Progress on Manganese-Based Nanostructures as Responsive MRI Contrast Agents. Chemistry - A European Journal 2019, 25 (2), 431-441. DOI: 10.1002/chem.201802851.
[13] An, K.; Kwon, S. G.; Park, M.; Na, H. B.; Baik, S.-I.; Yu, J. H.; Kim, D.; Son, J. S.; Kim, Y. W.; Song, I. C. Synthesis of uniform hollow oxide nanoparticles through nanoscale acid etching. Nano letters 2008, 8 (12), 4252-4258.
[14] Han, C.; Xu, H.; Wang, R.; Wang, K.; Dai, Y.; Liu, Q.; Guo, M.; Li, J.; Xu, K. Synthesis of a multifunctional manganese (II)–carbon dots hybrid and its application as an efficient magnetic-fluorescent imaging probe for ovarian cancer cell imaging. Journal of Materials Chemistry B 2016, 4 (35), 5798-5802.
[15] Bi, H.; Dai, Y.; Yang, P.; Xu, J.; Yang, D.; Gai, S.; He, F.; An, G.; Zhong, C.; Lin, J. Glutathione and H2O2 consumption promoted photodynamic and chemotherapy based on biodegradable MnO2–Pt@ Au25 nanosheets. Chemical Engineering Journal 2019, 356, 543-553.
[16] Abbasi, A. Z.; Prasad, P.; Cai, P.; He, C.; Foltz, W. D.; Amini, M. A.; Gordijo, C. R.; Rauth, A. M.; Wu, X. Y. Manganese oxide and docetaxel co-loaded fluorescent polymer nanoparticles for dual modal imaging and chemotherapy of breast cancer. Journal of controlled release 2015, 209, 186-196.
[17] Zhang, Y.; Zhang, C.; Chen, J.; Li, Y.; Yang, M.; Zhou, H.; Shahzad, S. A.; Qi, H.; Yu, C.; Jiang, S. A real-time fluorescence turn-on assay for acetylcholinesterase activity based on the controlled release of a perylene probe from MnO 2 nanosheets. Journal of Materials Chemistry C 2017, 5 (19), 4691-4694.
[18] Farrugia, A. Albumin usage in clinical medicine: tradition or therapeutic? Transfusion medicine reviews 2010, 24 (1), 53-63.
[19] He, X. M.; Carter, D. C. Atomic structure and chemistry of human serum albumin. Nature 1992, 358 (6383), 209-215.
[20] Green, M.; Manikhas, G.; Orlov, S.; Afanasyev, B.; Makhson, A.; Bhar, P.; Hawkins, M. Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Annals of oncology 2006, 17 (8), 1263-1268.
[21] Elzoghby, A. O.; Samy, W. M.; Elgindy, N. A. Albumin-based nanoparticles as potential controlled release drug delivery systems. Journal of controlled release 2012, 157 (2), 168-182.
[22] Jahanban-Esfahlan, A.; Panahi-Azar, V. Interaction of glutathione with bovine serum albumin: Spectroscopy and molecular docking. Food chemistry 2016, 202, 426-431.
[23] Vogel, S. M.; Minshall, R. D.; Pilipović, M.; Tiruppathi, C.; Malik, A. B. Albumin uptake and transcytosis in endothelial cells in vivo induced by albumin-binding protein. American Journal of Physiology-Lung Cellular and Molecular Physiology 2001, 281 (6), L1512-L1522. Desai, N.; Trieu, V.; Damascelli, B.; Soon-Shiong, P. SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Translational oncology 2009, 2 (2), 59-64.
[24] Simões, S.; Slepushkin, V.; Pires, P.; Gaspar, R.; De Lima, M. C. P.; Düzgüneş, N. Human serum albumin enhances DNA transfection by lipoplexes and confers resistance to inhibition by serum. Biochimica et Biophysica Acta (BBA)-Biomembranes 2000, 1463 (2), 459-469.
[25] Sahay, G.; Querbes, W.; Alabi, C.; Eltoukhy, A.; Sarkar, S.; Zurenko, C.; Karagiannis, E.; Love, K.; Chen, D.; Zoncu, R. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nature biotechnology 2013, 31 (7), 653-658.
[26] Cheema, M. A.; Taboada, P.; Barbosa, S.; Juárez, J.; Gutiérrez-Pichel, M.; Siddiq, M.; Mosquera, V. Human serum albumin unfolding pathway upon drug binding: A thermodynamic and spectroscopic description. The Journal of Chemical Thermodynamics 2009, 41 (4), 439-447.
[27] Jahanban-Esfahlan, A.; Ostadrahimi, A.; Jahanban-Esfahlan, R.; Roufegarinejad, L.; Tabibiazar, M.; Amarowicz, R. Recent developments in the detection of bovine serum albumin. Int J Biol Macromol 2019, 138, 602-617. DOI: 10.1016/j.ijbiomac.2019.07.096 From NLM Medline.
[28] Jeong, H.; Huh, M.; Lee, S. J.; Koo, H.; Kwon, I. C.; Jeong, S. Y.; Kim, K. Photosensitizer-conjugated human serum albumin nanoparticles for effective photodynamic therapy. Theranostics 2011, 1, 230.
[29] Sheng, Z.; Hu, D.; Zheng, M.; Zhao, P.; Liu, H.; Gao, D.; Gong, P.; Gao, G.; Zhang, P.; Ma, Y. Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy. ACS nano 2014, 8 (12), 12310-12322.
[30] Xie, J.; Zheng, Y.; Ying, J. Y. Protein-directed synthesis of highly fluorescent gold nanoclusters. Journal of the American Chemical Society 2009, 131 (3), 888-889.
[31] Huang, J.; Lin, L.; Sun, D.; Chen, H.; Yang, D.; Li, Q. Bio-inspired synthesis of metal nanomaterials and applications. Chemical Society Reviews 2015, 44 (17), 6330-6374.
[32] Kim, K. H.; Jeong, J.-M.; Lee, S. J.; Choi, B. G.; Lee, K. G. Protein-directed assembly of cobalt phosphate hybrid nanoflowers. Journal of Colloid and Interface Science 2016, 484, 44-50.
[33] Xie, J.; Lee, J. Y.; Wang, D. I. Synthesis of single-crystalline gold nanoplates in aqueous solutions through biomineralization by serum albumin protein. The Journal of Physical Chemistry C 2007, 111 (28), 10226-10232.
[34] Au, L.; Lim, B.; Colletti, P.; Jun, Y. S.; Xia, Y. Synthesis of gold microplates using bovine serum albumin as a reductant and a stabilizer. Chemistry–An Asian Journal 2010, 5 (1), 123-129.
[35] Goswami, N.; Giri, A.; Bootharaju, M.; Xavier, P. L.; Pradeep, T.; Pal, S. K. Copper quantum clusters in protein matrix: potential sensor of Pb2+ ion. Analytical chemistry 2011, 83 (24), 9676-9680.
[36] Cao, H.; Yang, D.-P.; Ye, D.; Zhang, X.; Fang, X.; Zhang, S.; Liu, B.; Kong, J. Protein-inorganic hybrid nanoflowers as ultrasensitive electrochemical cytosensing Interfaces for evaluation of cell surface sialic acid. Biosensors and Bioelectronics 2015, 68, 329-335.
[37] Zhuang, L.; Wang, W.; Hong, F.; Yang, S.; You, H.; Fang, J.; Ding, B. Porous platinum mesoflowers with enhanced activity for methanol oxidation reaction. Journal of Solid State Chemistry 2012, 191, 239-245.
[38] Hou, C.; Yang, D.; Liang, B.; Liu, A. Enhanced performance of a glucose/O2 biofuel cell assembled with laccase-covalently immobilized three-dimensional macroporous gold film-based biocathode and bacterial surface displayed glucose dehydrogenase-based bioanode. Analytical chemistry 2014, 86 (12), 6057-6063.
[39] Roelandts, R. The history of phototherapy: something new under the sun? Journal of the American Academy of Dermatology 2002, 46 (6), 926-930.
[40] Rathod, D. G.; Muneer, H.; Masood, S. Phototherapy. In StatPearls [Internet], StatPearls Publishing, 2021.
[41] Dolmans, D. E.; Fukumura, D.; Jain, R. K. Photodynamic therapy for cancer. Nature reviews cancer 2003, 3 (5), 380-387.
[42] Allison, R. R.; Bagnato, V. S.; Cuenca, R.; Downie, G. H.; Sibata, C. H. The future of photodynamic therapy in oncology. 2006.
[43] Meimandi, M.; Ardakani, M. R. T.; Nejad, A. E.; Yousefnejad, P.; Saebi, K.; Tayeed, M. H. The effect of photodynamic therapy in the treatment of chronic periodontitis: a review of literature. Journal of lasers in medical sciences 2017, 8 (Suppl 1), S7.
[44] Jeong, Y.; Jo, Y. K.; Kim, B. J.; Yang, B.; Joo, K. I.; Cha, H. J. Sprayable adhesive nanotherapeutics: mussel-protein-based nanoparticles for highly efficient locoregional cancer therapy. ACS nano 2018, 12 (9), 8909-8919.
[45] Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers in medical science 2008, 23 (3), 217-228.
[46] Vines, J. B.; Yoon, J.-H.; Ryu, N.-E.; Lim, D.-J.; Park, H. Gold nanoparticles for photothermal cancer therapy. Frontiers in chemistry 2019, 7, 167.
[47] Mitragotri, S. Introduction to special issue on “Nanoparticles in medicine: Targeting, optimization and clinical applications”. Bioengineering & Translational Medicine 2016, 1 (1), 8-9.
[48] Chen, W. R.; Adams, R. L.; Bartels, K. E.; Nordquist, R. E. Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser. Cancer Letters 1995, 94 (2), 125-131.
[49] Xia, B.; Wang, B.; Shi, J.; Zhang, Y.; Zhang, Q.; Chen, Z.; Li, J. Photothermal and biodegradable polyaniline/porous silicon hybrid nanocomposites as drug carriers for combined chemo-photothermal therapy of cancer. Acta Biomaterialia 2017, 51, 197-208.
[50] Wei, W.; Zhang, X.; Zhang, S.; Wei, G.; Su, Z. Biomedical and bioactive engineered nanomaterials for targeted tumor photothermal therapy: a review. Materials Science and Engineering: C 2019, 104, 109891.
[51] Liu, T.-M.; Conde, J.; Lipiński, T.; Bednarkiewicz, A.; Huang, C.-C. Smart NIR linear and nonlinear optical nanomaterials for cancer theranostics: Prospects in photomedicine. Progress in Materials Science 2017, 88, 89-135.
[52] Elbialy, N. S.; Fathy, M. M.; Reem, A.-W.; Darwesh, R.; Abdel-Dayem, U. A.; Aldhahri, M.; Noorwali, A.; Al-Ghamdi, A. A. Multifunctional magnetic-gold nanoparticles for efficient combined targeted drug delivery and interstitial photothermal therapy. International journal of pharmaceutics 2019, 554, 256-263.
[53] Zha, Z.; Yue, X.; Ren, Q.; Dai, Z. Uniform polypyrrole nanoparticles with high photothermal conversion efficiency for photothermal ablation of cancer cells. Advanced materials 2013, 25 (5), 777-782.
[54] Luby, B. M.; Walsh, C. D.; Zheng, G. Advanced photosensitizer activation strategies for smarter photodynamic therapy beacons. Angewandte Chemie International Edition 2019, 58 (9), 2558-2569.
[55] Kwiatkowski, S.; Knap, B.; Przystupski, D.; Saczko, J.; Kędzierska, E.; Knap-Czop, K.; Kotlińska, J.; Michel, O.; Kotowski, K.; Kulbacka, J. Photodynamic therapy–mechanisms, photosensitizers and combinations. Biomedicine & Pharmacotherapy 2018, 106, 1098-1107.
[56] Niculescu, A.-G.; Grumezescu, A. M. Photodynamic Therapy—An Up-to-Date Review. Applied Sciences 2021, 11 (8). DOI: 10.3390/app11083626.
[57] Alves, C. G.; Lima-Sousa, R.; de Melo-Diogo, D.; Louro, R. O.; Correia, I. J. IR780 based nanomaterials for cancer imaging and photothermal, photodynamic and combinatorial therapies. Int J Pharm 2018, 542 (1-2), 164-175. DOI: 10.1016/j.ijpharm.2018.03.020 From NLM Medline.
[58] Cheng, Y.; Cheng, H.; Jiang, C.; Qiu, X.; Wang, K.; Huan, W.; Yuan, A.; Wu, J.; Hu, Y. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy. Nature communications 2015, 6 (1), 1-8.
[59] von Roemeling, C.; Jiang, W.; Chan, C. K.; Weissman, I. L.; Kim, B. Y. Breaking down the barriers to precision cancer nanomedicine. Trends in biotechnology 2017, 35 (2), 159-171.
[60] Chen, Y.; Li, Z.; Wang, H.; Wang, Y.; Han, H.; Jin, Q.; Ji, J. IR-780 loaded phospholipid mimicking homopolymeric micelles for near-IR imaging and photothermal therapy of pancreatic cancer. ACS applied materials & interfaces 2016, 8 (11), 6852-6858.
[61] He, B.; Hu, H.-y.; Tan, T.; Wang, H.; Sun, K.-x.; Li, Y.-p.; Zhang, Z.-w. IR-780-loaded polymeric micelles enhance the efficacy of photothermal therapy in treating breast cancer lymphatic metastasis in mice. Acta Pharmacologica Sinica 2018, 39 (1), 132-139.
[62] Tang, Z.; Liu, Y.; He, M.; Bu, W. Chemodynamic therapy: tumour microenvironment‐mediated Fenton and Fenton‐like reactions. Angewandte Chemie International Edition 2019, 58 (4), 946-956.
[63] Ren, Z.; Sun, S.; Sun, R.; Cui, G.; Hong, L.; Rao, B.; Li, A.; Yu, Z.; Kan, Q.; Mao, Z. A metal–polyphenol‐coordinated nanomedicine for synergistic cascade cancer chemotherapy and chemodynamic therapy. Advanced Materials 2020, 32 (6), 1906024.
[64] Szatrowski, T. P.; Nathan, C. F. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer research 1991, 51 (3), 794-798.
[65] Song, X.; Xu, J.; Liang, C.; Chao, Y.; Jin, Q.; Wang, C.; Chen, M.; Liu, Z. Self-supplied tumor oxygenation through separated liposomal delivery of H2O2 and catalase for enhanced radio-immunotherapy of cancer. Nano letters 2018, 18 (10), 6360-6368.
[66] Fan, J. X.; Peng, M. Y.; Wang, H.; Zheng, H. R.; Liu, Z. L.; Li, C. X.; Wang, X. N.; Liu, X. H.; Cheng, S. X.; Zhang, X. Z. Engineered bacterial bioreactor for tumor therapy via Fenton‐like reaction with localized H2O2 generation. Advanced Materials 2019, 31 (16), 1808278.
[67] Zhang, L.; Wan, S.-S.; Li, C.-X.; Xu, L.; Cheng, H.; Zhang, X.-Z. An adenosine triphosphate-responsive autocatalytic fenton nanoparticle for tumor ablation with self-supplied H2O2 and acceleration of Fe (III)/Fe (II) conversion. Nano letters 2018, 18 (12), 7609-7618.
[68] Xu, R.; Xu, Z.; Si, Y.; Xing, X.; Li, Q.; Xiao, J.; Wang, B.; Tian, G.; Zhu, L.; Wu, Z. Oxygen vacancy defect-induced activity enhancement of Gd doping magnetic nanocluster for oxygen supplying cancer theranostics. ACS Applied Materials & Interfaces 2020, 12 (33), 36917-36927.
[69] Zhang, C.; Bu, W.; Ni, D.; Zhang, S.; Li, Q.; Yao, Z.; Zhang, J.; Yao, H.; Wang, Z.; Shi, J. Synthesis of iron nanometallic glasses and their application in cancer therapy by a localized Fenton reaction. Angewandte Chemie 2016, 128 (6), 2141-2146.
[70] Hu, P.; Wu, T.; Fan, W.; Chen, L.; Liu, Y.; Ni, D.; Bu, W.; Shi, J. Near infrared-assisted Fenton reaction for tumor-specific and mitochondrial DNA-targeted photochemotherapy. Biomaterials 2017, 141, 86-95.
[71] Nie, Y.; Li, D.; Peng, Y.; Wang, S.; Hu, S.; Liu, M.; Ding, J.; Zhou, W. Metal organic framework coated MnO2 nanosheets delivering doxorubicin and self-activated DNAzyme for chemo-gene combinatorial treatment of cancer. International Journal of Pharmaceutics 2020, 585, 119513. Ding, B.; Shao, S.; Jiang, F.; Dang, P.; Sun, C.; Huang, S.; Ma, P. a.; Jin, D.; Kheraif, A. A. A.; Lin, J. MnO2-disguised upconversion hybrid nanocomposite: an ideal architecture for tumor microenvironment-triggered UCL/MR bioimaging and enhanced chemodynamic therapy. Chemistry of Materials 2019, 31 (7), 2651-2660.
[72] Fu, L.-H.; Hu, Y.-R.; Qi, C.; He, T.; Jiang, S.; Jiang, C.; He, J.; Qu, J.; Lin, J.; Huang, P. Biodegradable manganese-doped calcium phosphate nanotheranostics for traceable cascade reaction-enhanced anti-tumor therapy. ACS nano 2019, 13 (12), 13985-13994.
[73] Cao, S.; Fan, J.; Sun, W.; Li, F.; Li, K.; Tai, X.; Peng, X. A novel Mn–Cu bimetallic complex for enhanced chemodynamic therapy with simultaneous glutathione depletion. Chemical Communications 2019, 55 (86), 12956-12959.
[74] Primo, O.; Rivero, M. J.; Ortiz, I. Photo-Fenton process as an efficient alternative to the treatment of landfill leachates. Journal of hazardous materials 2008, 153 (1-2), 834-842.
[75] Liu, Y.; Zhen, W.; Wang, Y.; Liu, J.; Jin, L.; Zhang, T.; Zhang, S.; Zhao, Y.; Song, S.; Li, C. One‐dimensional Fe2P acts as a Fenton agent in response to NIR II light and ultrasound for deep tumor synergetic theranostics. Angewandte Chemie 2019, 131 (8), 2429-2434.
[76] An, P.; Fan, F.; Gu, D.; Gao, Z.; Hossain, A. M. S.; Sun, B. Photothermal-reinforced and glutathione-triggered in Situ cascaded nanocatalytic therapy. Journal of Controlled Release 2020, 321, 734-743.
[77] Ying, W.; Zhang, Y.; Gao, W.; Cai, X.; Wang, G.; Wu, X.; Chen, L.; Meng, Z.; Zheng, Y.; Hu, B. Hollow magnetic nanocatalysts drive starvation–chemodynamic–hyperthermia synergistic therapy for tumor. ACS nano 2020, 14 (8), 9662-9674.
[78] Wong, C. M.; Wong, K. H.; Chen, X. D. Glucose oxidase: natural occurrence, function, properties and industrial applications. Applied microbiology and biotechnology 2008, 78 (6), 927-938.
[79] Bankar, S. B.; Bule, M. V.; Singhal, R. S.; Ananthanarayan, L. Glucose oxidase—an overview. Biotechnology advances 2009, 27 (4), 489-501.
[80] Zhao, W.; Hu, J.; Gao, W. Glucose oxidase–polymer nanogels for synergistic cancer-starving and oxidation therapy. ACS applied materials & interfaces 2017, 9 (28), 23528-23535.
[81] Zhang, R.; Feng, L.; Dong, Z.; Wang, L.; Liang, C.; Chen, J.; Ma, Q.; Chen, Q.; Wang, Y.; Liu, Z. Glucose & oxygen exhausting liposomes for combined cancer starvation and hypoxia-activated therapy. Biomaterials 2018, 162, 123-131.
[82] Maddocks, O. D.; Berkers, C. R.; Mason, S. M.; Zheng, L.; Blyth, K.; Gottlieb, E.; Vousden, K. H. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013, 493 (7433), 542-546.
[83] Wang, C.; Ye, Y.; Hochu, G. M.; Sadeghifar, H.; Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PD1 antibody. Nano letters 2016, 16 (4), 2334-2340.
[84] Chang, K.; Liu, Z.; Fang, X.; Chen, H.; Men, X.; Yuan, Y.; Sun, K.; Zhang, X.; Yuan, Z.; Wu, C. Enhanced phototherapy by nanoparticle-enzyme via generation and photolysis of hydrogen peroxide. Nano Letters 2017, 17 (7), 4323-4329.
[85] Wang, L.; Xu, X.; Mu, X.; Han, Q.; Liu, J.; Feng, J.; Zhang, P.; Yuan, Q. Fe-doped copper sulfide nanoparticles for in vivo magnetic resonance imaging and simultaneous photothermal therapy. Nanotechnology 2019, 30 (41), 415101.
[86] Foroozandeh, P.; Aziz, A. A. Insight into cellular uptake and intracellular trafficking of nanoparticles. Nanoscale research letters 2018, 13 (1), 1-12.