Interfering with Lactate-Fueled Respiration for Enhanced Photodynamic Tumor Therapy by a Porphyrinic MOF Nanoplatform
Interfering with Lactate-Fueled Respiration for Enhanced Photodynamic Tumor Therapy by a Porphyrinic MOF Nanoplatform
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DOI：
10.1002/adfm.201803498
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发表时间：
2018-09-05
影响因子：
19
通讯作者：
Zhang, Xian-Zheng
中科院分区：
文献类型：
--
作者：
Chen, Zhao-Xia;Liu, Miao-Deng;Zhang, Xian-Zheng
乳酸是氧化肿瘤细胞的重要能量底物。干扰氧化肿瘤细胞以乳酸为燃料的呼吸将是一种很有前途的癌症治疗策略。在本研究中，将α -氰基-4-羟基肉桂酸（CHC）加入到多孔Zr （IV）基卟啉金属有机框架（PZM）纳米颗粒中，通过抑制肿瘤细胞中乳酸-质子同体、单羧酸转运蛋白1 （MCT1）的表达来减少乳酸的摄取，从而将乳酸为燃料的有氧呼吸转化为厌氧糖酵解。能量供应的改变还可以减少肿瘤细胞的耗氧量，从而促进光动力疗法（PDT）在癌症治疗中的应用。此外，透明质酸（HA）被包裹在PZM纳米颗粒表面，用于靶向cd44和透明质酸酶诱导的细胞内药物释放。体外和体内研究均证实，ha包被的PZM纳米颗粒（CHC-PZM@HA）在肿瘤细胞中具有良好的生物相容性和增强的PDT效果。CHC-PZM@HA平台将为癌症治疗提供新的视角。
Lactate is a prominent energy substrate for oxidative tumor cells. Interfering with the lactate-fueled respiration of oxidative tumor cells would be a promising therapeutic strategy for cancer treatment. In this study, alpha-cyano-4-hydroxycinnamate (CHC) is incorporated into a porous Zr (IV)-based porphyrinic metal-organic framework (PZM) nanoparticle, to reduce the lactate uptake by inhibiting the expression of lactate-proton symporter, monocarboxylate transporter 1 (MCT1) in tumor cells, thus transform lactate-fueled aerobic respiration to anaerobic glycolysis. The alteration in energy supply can also decrease the oxygen consumption in tumor cells, which would facilitate the photodynamic therapy (PDT) in cancer treatment. Moreover, hyaluronic acid (HA) is coated on the surface of PZM nanoparticles for CD44-targeting and hyaluronidase-induced intracellular drug releasing. Both in vitro and in vivo studies confirmed good biocompatibility and enhanced PDT efficacy of the HA-coated PZM nanoparticles (CHC-PZM@HA) in tumor cells. The CHC-PZM@HA platform will provide a new perspective in cancer therapy.