School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu 226019, China.
J Mater Chem B. 2021 Feb 14;9(6):1698-1706. doi: 10.1039/d0tb02626c. Epub 2021 Jan 26.
The overexpression of P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells increases the efflux of anticancer drugs thereby causing the failure of clinical chemotherapy. To address this obstacle, in this study, we rationally designed a near-infrared (NIR) light-responsive nitric oxide (NO) delivery nanoplatform for targeting the MDR tumors based on core-shell structured nanocomposites. The mesoporous silica shell provided abundant sites for modification of the NO donor, N-diazeniumdiolate, and tumor-targeting molecule, folic acid (FA), and enabled high encapsulation capacity for doxorubicin (DOX) loading. Under NIR light irradiation, the generation of NO gas can efficiently augment chemotherapeutic effects via the inhibition of P-gp expression. Simultaneously, the photothermal conversion agents of the CuSe core produce a large amount of heat for photothermal therapy (PTT). Finally, this combinational gas/chemo/PTT not only displays a superior and synergistic effect for overcoming MDR cancer, but also provides an efficient strategy to construct a multifunctional nano-drug delivery system with diversified therapeutic modalities.
多药耐药（MDR）癌细胞中 P-糖蛋白（P-gp）的过度表达会增加抗癌药物的外排，从而导致临床化疗失败。为了解决这一障碍，在本研究中，我们基于核壳结构的纳米复合材料，合理设计了一种近红外（NIR）光响应一氧化氮（NO）递药纳米平台，用于靶向 MDR 肿瘤。介孔硅壳为 NO 供体 N-二亚硝基脒（N-diazeniumdiolate）和肿瘤靶向分子叶酸（FA）的修饰提供了丰富的位点，并实现了阿霉素（DOX）的高载药量。在近红外光照射下，NO 气体的产生可以通过抑制 P-gp 的表达，有效地增强化疗效果。同时，CuSe 核的光热转换剂会产生大量热量用于光热治疗（PTT）。最后，这种联合的气体/化疗/PTT 不仅显示出克服 MDR 癌症的优异协同作用，而且为构建具有多种治疗方式的多功能纳米药物递送系统提供了一种有效的策略。
