金纳米棒（Au NR）是一种用于肿瘤治疗的有价值的光热纳米材料。然而，当用Au NRs进行光热治疗时，肿瘤中热休克蛋白的表达会增加，从而诱导肿瘤细胞产生耐热性，降低Au NRs的光热治疗效果。通过RNA干扰，有效抑制热休克蛋白的表达，提高肿瘤光热治疗的疗效。然而，深层且非侵入性的组织渗透仍然是成功应用 siRNA 的巨大障碍。因此，纳米平台 AGC/HSP-70 siRNA 被设计用于通过 RNA 干扰增强光热肿瘤治疗。在AGC/HSP-70 siRNA复合物中，Au-S键修饰了金纳米棒表面的基质金属蛋白酶2（MMP-2）敏感肽GPLGLAG。此外，天然碱性多糖（壳聚糖）通过酰胺键与肽反应，以递送热休克蛋白70沉默siRNA（HSP-70 siRNA）。修饰MMP-2敏感的​​连接子可以导致更多的Au NR在肿瘤中积累，发挥光热效应，促进HSP-70 siRNA和壳聚糖复合物渗透到肿瘤组织深处。体外实验表明，AGC/HSP-70 siRNA 的 MMP-2 敏感接头的酶解可促进肿瘤细胞中 HSP-70 siRNA 的细胞摄取和核周分布，这可能是由于其尺寸较小且带正电。的复合物。所有这些结果确保了HSP-70 siRNA的有效基因沉默作用，以增强Au NRs在肿瘤组织中的光热治疗效果，正如基因沉默和细胞凋亡实验所证明的那样。体内实验进一步证明AGC/HSP-70 siRNA纳米平台有效提高了Au NRs的光热效应。总之，这项工作证明AGC/HSP-70 siRNA是一种有前途的药物递送策略，通过调节深部肿瘤细胞的光热敏感性以及在肿瘤组织中保留更多的Au NR来增强肿瘤的光热治疗，并提供了一种新的药物递送策略。肿瘤光热治疗的新策略。

Gold nanorods (Au NRs) are a valuable photothermal nanomaterial for tumor therapy. However, when treated with Au NRs for photothermal therapy, the expression of heat shock proteins in tumors will increase, which will induce heat resistance in tumor cells and reduce the photothermal therapeutic effect of Au NRs. By RNA interference, the expression of heat shock proteins would be effectively inhibited to improve the efficasy of tumor photothermal therapy. However, deep and noninvasive tissue penetration remains a great obstacle to applying siRNA successfully. Thus, the nanoplatform AGC/HSP-70 siRNA was designed for enhanced photothermal tumor therapy by RNA interference. In the AGC/HSP-70 siRNA complex, the Au-S bond modified the matrix metalloproteinase-2 (MMP-2)-sensitive peptide GPLGLAG on the surface of gold nanorods. Moreover, the natural basic polysaccharide (chitosan) was reacted with the peptide by an amide bond for delivering heat shock protein 70 silencing siRNA (HSP-70 siRNA). Modifying the MMP-2-sensitive linker could cause more Au NRs to accumulate in tumors to exert a photothermal effect and promote the penetration of HSP-70 siRNA and chitosan complexes into deep tumor tissues. In vitro experiments indicated that the enzymolysis of the MMP-2-sensitive linker for AGC/HSP-70 siRNA could promote the cellular uptake and perinuclear distribution of HSP-70 siRNA in tumor cells, which may be due to the smaller size and positive electricity of the complexes. All of these results ensured the efficient gene silencing effect of HSP-70 siRNA to enhance the photothermal therapeutic effect of Au NRs in tumor tissues, as demonstrated by the gene silencing and cellular apoptotic experiments. In vivo experiments further proved that the AGC/HSP-70 siRNA nanoplatform efficiently improved the photothermal effect of Au NRs. In summary, this work proved that AGC/HSP-70 siRNA is a promising drug delivery strategy for enhancing the photothermal therapy of tumors by regulating the photothermal sensitivity of deep tumor cells as well as retaining more Au NRs in tumor tissues, and also provides a novel strategy for tumor photothermal therapy.