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Carbon Dots-Based Nanozyme for Drug-Resistant Lung Cancer Therapy by Encapsulated Doxorubicin/siRNA Cocktail

作者:Hailing Yu, Kexin Tang, Zeyu Cai, Xi Lin, Yongquan Huang, Ting Yu, Qianqian Zhang, Qiang Wang, Lili Wu, Lei Yang, Hong Shan, Hui Luo · 发表于:International Journal of Nanomedicine · 年份:2023 · DOI:10.2147/ijn.s390984 · 被引用次数:49 · 研究领域:Advanced Nanomaterials in Catalysis、Carbon and Quantum Dots Applications、Nanoplatforms for cancer theranostics

Background: Nanomaterials exhibited intrinsic enzyme-like properties due to the unique properties compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. Carbon dots possess intrinsic enzyme-like properties, such as glutathione (GSH) oxidase or peroxidase activities. Methods: A co-delivery nanosystem that could carry siRNA and doxorubucin (DOX) simultaneously has been studied in this work. The co-delivery based on carbon dots was surface-modified with poly-ethylenimine (PEI) and loaded the siMRP1 with chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI was raw materials and passivator during the reaction process that makes CDs exhibit excellent optical property. Results: The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumors and releasing them synchronously in cells in an acid-triggered manner. The particles exhibited GSH oxidase-like catalytic property, oxidizing GSH to oxidized glutathione with concomitant increase of reactive oxygen species (ROS). We found that silencing of MRP1 by co-delivery system antagonized chemoresistance by increasing DOX accumulation and significantly enhancing the inhibitory effect of cell viability induced by CD-PEI-DOX. The co-delivery system dramatically inhibited tumor growth in xenograft model, and CDs cou...