Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross‐resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid‐labile hydrazone bond. Stimulated by the acidic media in endocytic organelles, DOX@FG exhibited a responsive dissociation for the controlled release of chemotherapeutic DOX. Surprisingly, we found the mild photothermal effect elicited by GNRs under NIR irradiation simultaneously inhibited the pump and nonpump resistance mechanisms, enhancing the intracellular DOX accumulation and sensitizing the cancer cells to DOX, collectively amplify the chemotherapy efficacy and delay the MCF‐7/ADR breast tumor growth. This intelligent DOX@FG nanomedicine with the potential for two‐pronged reversal of MDR may provide a prospective way to encourage chemotherapy efficacy.

中文翻译：

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金纳米棒双管齐下逆转化疗耐药性诱导轻度光热效应


化疗治疗结果受到多药耐药 （MDR） 的严重限制，其中肿瘤对涉及泵和非泵耐药机制的药物产生多重交叉耐药，导致药物外流并防御药物毒性。在此，我们构建了一种基于金纳米棒 （GNR） 的 pH 和近红外 （NIR） 光响应纳米药物DOX@FG，该纳米药物证明了通过克服 MDR 来改善化疗结果的潜力。DOX@FG 是通过将叶酸 （FA） 和阿霉素 （DOX） 衍生物偶联到 GNR 上构建的，其中 DOX 衍生物具有不稳定的酸腙键。在内吞细胞器中酸性介质的刺激下，DOX@FG 表现出对化疗 DOX 控制释放的反应性解离。令人惊讶的是，我们发现 GNRs 在 NIR 照射下引发的温和光热效应同时抑制泵和非泵阻力机制，增强细胞内 DOX 积累并使癌细胞对 DOX 敏感，共同放大化疗疗效并延缓 MCF-7/ADR 乳腺肿瘤生长。这种智能DOX@FG纳米药物具有双管齐下逆转 MDR 的潜力，可能为促进化疗疗效提供一种前瞻性方法。