多重耐药
光热治疗
化疗
癌症研究
MTT法
癌症
流式细胞术
免疫印迹
纳米医学
阿霉素
癌细胞
材料科学
体外
医学
生物医学工程
化学
纳米技术
免疫学
抗药性
纳米颗粒
生物
外科
内科学
微生物学
生物化学
基因
作者
Yue Ding,Chang Du,Jiwen Qian,Chang‐Ming Dong
出处
期刊:Nano Letters
[American Chemical Society]
日期:2019-06-14
卷期号:19 (7): 4362-4370
被引量:133
标识
DOI:10.1021/acs.nanolett.9b00975
摘要
Multidrug resistance (MDR) of cancers that results from overexpression of a P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypeptide nanomedicines. Herein, a novel polypeptide nanocomposite PNOC-PDA that integrates heat-sensitive NO gas delivery and photothermal conversion attributes can overcome MDR and maximize CT; meanwhile the optimized CT and intracellular high-concentration NO gas can assist a mild photothermal therapy (PTT) to eradicate cancer cells. The triple therapies produced a superior and synergistic effect on MDR-reversal and killing MCF-7/ADR in vitro, and the P-gp expression level was downregulated to 46%, as confirmed by means of MTT, Western blot, flow cytometry, and confocal laser scanning microscopy. Significantly, by using one intravenous injection of PNOC-PDA/DOX and a single near-infrared irradiation, the triple therapies of mild PTT, NO gas therapy, and CT achieved complete MCF-7/ADR tumor ablation without skin damage, scarring, and tumor recurrence within 30 days. This work provides a versatile method for the fabrication of NIR-responsive polypeptide nanocomposite with intrinsic photothermal conversion and NO-releasing attributes, opening up a new avenue for reversing MDR in tumors.
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