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Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells
Pharmaceutics ( IF 5.4 ) Pub Date : 2020-10-09 , DOI: 10.3390/pharmaceutics12100950
Imran Shair Mohammad , Birendra Chaurasiya , Xuan Yang , Chuchu Lin , Hehui Rong , Wei He

“Off-targeting” and receptor density expressed at the target sites always compromise the efficacy of the nanoparticle-based drug delivery systems. In this study, we isolated different cell membranes and constructed cell membrane-cloaked biogenic nanoparticles for co-delivery of antitumor paclitaxel (PTX) and multidrug resistance (MDR)-modulator disulfiram (DSF). Consequently, MDR cancer cell membrane (A549/T)-coated hybrid nanoparticles (A549/T CM-HNPs) selectively recognized the source cells and increased the uptake by ninefold via the homotypic binding mechanism. Moreover, the A549/T CM-HNPs sensitized MDR cells to PTX by suppressing P-glycoprotein (P-gp) activity by 3.2-fold and induced effective apoptosis (70%) in homologous A549/T cells. Cell-membrane coating based on the “homotypic binding” is promising in terms of promoting the accumulation of chemotherapeutics in MDR cells and killing them.

中文翻译:

以同种型为目标的生物纳米颗粒杀死耐多药的癌细胞

在靶位点表达的“脱靶”和受体密度总是损害基于纳米颗粒的药物递送系统的功效。在这项研究中,我们分离了不同的细胞膜,并构建了细胞膜隐蔽的生物纳米颗粒,用于共同递送抗肿瘤紫杉醇(PTX)和多药耐药性(MDR)调节剂双硫仑(DSF)。因此,涂有MDR癌细胞膜(A549 / T)的杂化纳米颗粒(A549 / T CM-HNPs)通过同型结合机制选择性地识别了源细胞并增加了9倍的摄取。此外,A549 / T CM-HNP通过将P-糖蛋白(P-gp)活性抑制3.2倍,使MDR细胞对PTX敏感,并在同源A549 / T细胞中诱导有效的细胞凋亡(70%)。
更新日期:2020-10-11
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