School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, PR China.
School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, PR China.
Acta Biomater. 2021 Mar 15;123:335-345. doi: 10.1016/j.actbio.2021.01.015. Epub 2021 Jan 18.
Multidrug resistance (MDR) induced by the overexpression of P-glycoprotein (P-gp) transporters mainly leads to chemotherapy (CT) failure. Herein, a NIR/pH dual-sensitive charge-reversal polypeptide nanocomposite (PDA-PLC) was developed for co-delivering a nitric oxide (NO) donor and doxorubicin (DOX). Under near-infrared (NIR) irradiation, the released high-concentration of NO gas inhibited the P-gp expression to sensitize the chemotherapeutic medicine DOX and assisted photothermal therapy (PTT) to eradicate cancer cells without skin scarring. Further, the distinctive charge-reversal capacity of PDA-PLC significantly facilitated cellular uptake in the tumor acidic microenvironment (pH 6.8) and enhanced its stability in the physiological environment (pH 7.4). This DOX-loading polypeptide nanocomposite (PDA-PLC/DOX) provides an effective strategy for the PTT-NO-CT triple-combination therapy to overcome MDR STATEMENT OF SIGNIFICANCE: Multidrug resistance (MDR) has been considered to be the paramount factor of chemotherapy (CT) failure in cancer. In this work, an NIR/pH dual-sensitive charge-reversal polypeptide nanomedicine (PDA-PLC/DOX) was developed to overcome MDR through the triple combination therapy of photothermal therapy (PTT), NO gas therapy, and CT. The distinctive charge-reversal capacity of PDA-PLC/DOX significantly facilitated cellular uptake in the tumor acidic microenvironment (pH 6.8) and enhanced its stability in the physiological environment (pH 7.4), while the NIR trigger-released NO gas greatly inhibited the expression of P-gp and synergistically enhanced PTT and CT efficacy. This polypeptide nanocomposite PDA-PLC/DOX provides an effective strategy of using the PTT-NO-CT triple combination therapy with charge-reversal property to completely eradicate the MCF-7/ADR tumor.
多药耐药（MDR）是导致化疗（CT）失败的主要原因，其是由 P-糖蛋白（P-gp）转运体的过度表达引起的。在此，开发了一种近红外（NIR）/pH 双重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）。在近红外（NIR）照射下，释放的高浓度 NO 气体抑制了 P-gp 的表达，使化疗药物 DOX 敏感，并辅助光热治疗（PTT）以消除癌细胞而不会留下皮肤疤痕。此外，PDA-PLC 的独特电荷反转能力显著促进了肿瘤酸性微环境（pH 6.8）中的细胞摄取，并增强了其在生理环境（pH 7.4）中的稳定性。这种 DOX 负载多肽纳米复合材料（PDA-PLC/DOX）为克服 MDR 的 PTT-NO-CT 三重联合治疗提供了一种有效策略。
多药耐药（MDR）被认为是癌症化疗（CT）失败的首要因素。在这项工作中，开发了一种近红外（NIR）/pH 双重敏感电荷反转多肽纳米医学（PDA-PLC/DOX），通过光热治疗（PTT）、NO 气体治疗和 CT 的三重联合治疗来克服 MDR。PDA-PLC/DOX 的独特电荷反转能力显著促进了肿瘤酸性微环境（pH 6.8）中的细胞摄取，并增强了其在生理环境（pH 7.4）中的稳定性，而 NIR 触发释放的 NO 气体则极大地抑制了 P-gp 的表达，并协同增强了 PTT 和 CT 疗效。这种多肽纳米复合材料 PDA-PLC/DOX 提供了一种有效的策略，即利用具有电荷反转特性的 PTT-NO-CT 三重联合治疗来彻底根除 MCF-7/ADR 肿瘤。
