Jiang Linping, Wang Kesi, Qiu Liyan
Ministry of Educational (MOE) Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Asian J Pharm Sci. 2022 Nov;17(6):924-937. doi: 10.1016/j.ajps.2022.10.006. Epub 2022 Nov 15.
Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics. The newly emerging role of nitric oxide (NO) to conquer drug resistance has been recognized as a potential strategy. However, it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites. Herein, we developed a PEGylated indocyanine green (mPEG-ICG) integrated nanovesicle system (PIDA) to simultaneously load doxorubicin hydrochloride (DOX⋅HCl) and the NO donor L-arginine (L-Arg), which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers. Upon 808 nm irradiation, the NO released from PIDA led to a decrease in mitochondrial membrane potential, an increase in ROS and significant ATP depletion in K562/ADR cells, thus inhibiting cell growth and resolving the problem of drug resistance. Consequently, the experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%. Above all, PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.
耐药性是临床上化疗效果不佳的原因。一氧化氮（NO）在克服耐药性方面新出现的作用已被视为一种潜在策略。然而，实现NO在所需部位的靶向递送以及精确释放仍然是一个巨大的挑战。在此，我们开发了一种聚乙二醇化吲哚菁绿（mPEG-ICG）集成纳米囊泡系统（PIDA），以同时负载盐酸多柔比星（DOX⋅HCl）和NO供体L-精氨酸（L-Arg），其可通过近红外光照射产生NO，并发挥多模态疗法使耐药癌症致敏。在808 nm照射下，PIDA释放的NO导致K562/ADR细胞线粒体膜电位降低、ROS增加和显著的ATP消耗，从而抑制细胞生长并解决耐药问题。因此，对携带K562/ADR的裸鼠进行的实验表明，PIDA纳米囊泡实现了显著的抗癌效果，肿瘤抑制率为80.8%。最重要的是，PIDA纳米囊泡为设计用于治疗耐药癌症的纳米平台提供了指导。
