期刊
NANO LETTERS
卷 19, 期 7, 页码 4362-4370出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b00975
关键词
Near-infrared; NO gas therapy; multidrug resistance; combination therapy; synergistic effect
类别
资金
- National Natural Science Foundation of China [21774074, 21474061]
- innovation program of Shanghai Municipal Education Commission [201701070002E0061]
- Innovation Fund of Shanghai Jiao Tong University and Affiliated Sixth People's Hospital South Campus [IFPM2016B004]
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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