Yue Ding, Yuxuan Ma, Chang Du, Chenwei Wang, Tingting Chen, Yang Wang, Jin Wang, Yong Yao, Changming Dong
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引用次数: 0
摘要
p -糖蛋白(P-gp)转运体过度表达引起的多药耐药(MDR)是化疗(CT)失败的主要原因。本文研制了一种新型的近红外/pH双敏感电荷反转多肽纳米复合材料(PDA-PLC)，用于共递送一氧化氮(NO)供体和阿霉素(DOX)。在智能近红外(NIR)照射下，释放的高浓度NO可以抑制P-gp的表达，逆转MDR，并辅助光热疗法(PTT)根除癌细胞而不留下皮肤疤痕。同时，PDA-PLC独特的电荷反转能力显著促进了肿瘤酸微环境(pH 6.8)下的细胞摄取，增强了其在生理环境(pH 7.4)下的稳定性。这种负载DOX的多肽纳米复合材料PDA-PLC/DOX为PTT-NO-CT三联治疗提供了克服MDR的有效策略。
Nir/Ph Dual-Sensitive Polypeptide Nanocomposite Charge-Reverse, Generates No for Triple-Combination Therapy to Reverse Cancer Multidrug Resistance
The multidrug resistance (MDR) induced by the overexpression of P-glycoprotein (P-gp) transporters mainly leads to the chemotherapy (CT) failure. Herein, a novel NIR/pH dual-sensitive charge-reversal polypeptide nanocomposite (PDA-PLC) was developed for co-delivering nitric oxide (NO) donor and doxorubicin (DOX). Under intelligent near-infrared (NIR) irradiation, the released high-concentration NO could inhibit the P-gp expression to reverse MDR, and assist photothermal therapy (PTT) to eradicate cancer cells without skin scarring. Meanwhile, the distinctive charge-reversal capacity of PDA-PLC significantly facilitates the cellular uptake at tumor acid microenvironment (pH 6.8) and enhances its stability at physiological environment (pH 7.4). This DOX-loading polypeptide nanocomposites PDA-PLC/DOX provide an effective strategy for the PTT-NO-CT triple-combination therapy to overcome MDR.
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