Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with high silencing efficiency which is even better than that of commercial Lipofectamine 2000. The in vitro and in vivo studies demonstrate the ability of the GNRs-siRNA nanoplex to sensitize the cancer cells to PTT under moderate laser irradiation by down-regulating the increased BAG3 expression and enhancing apoptosis. The GNRs-siRNA mediated PTT has large potential in clinical cancer therapy due to the elimination of therapeutic resistance and enhanced photothermal therapeutic efficacy by means of gene silencing. It also suggests an efficient platform for gene delivery and controllable gene therapy.

中文翻译：

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Gold-nanorods-siRNA纳米复合物通过基因沉默改善光热疗法

纳米材料介导的光热疗法（PTT）通常遭受热休克反应的基本细胞防御机制，这导致癌细胞的治疗抗性并降低治疗功效。在此，产生具有基因沉默能力的金纳米棒（GNRs）-siRNA平台以提高PTT效率。表面修饰后，GNRs表现出递送靶向BAG3的siRNA寡核苷酸的能力，BAG3是阻断热休克反应的有效基因。合成的GNRs-siRNA纳米复合物具有出色的将siRNA传递到癌细胞中的能力，具有很高的沉默效率，甚至比商用Lipofectamine 2000更好。体外和体内研究表明，GNRs-siRNA纳米复合物通过下调增加的BAG3表达和增强细胞凋亡在中等激光照射下使癌细胞对PTT敏感的能力。由于通过基因沉默消除了治疗抗性并增强了光热治疗功效，GNRs-siRNA介导的PTT在临床癌症治疗中具有巨大潜力。这也为基因传递和可控基因治疗提供了一个有效的平台。