An aptamer-conjugated gold nanostar (dsDDA-AuNS) has been developed for targeting nucleolin present in both tumor cells and tumor vasculature for conducting a drug-resistant cancer therapy. AuNS with its strong absorption in the near-infrared (NIR) region was assembled with a layer of the anti-nucleolin aptamer AS1411. An anticancer drug, namely doxorubicin (DOX), was specifically conjugated on deoxyguanosine residues employing heat and acid labile methylene linkages. In response to NIR irradiation, dsDDA-AuNS allowed on-demand therapeutics. AS1411 played an active role in drug cargo-nucleus interactions, enhancing drug accumulation in the nuclei of drug-resistant breast cancer cells. The intravenous injection of dsDDA-AuNS allowed higher drug accumulation in drug-resistant tumors over naked drugs, leading to greater therapeutic efficacy even at a 54-fold less equivalent drug dose. The in vivo triggered release of DOX from dsDDA-AuNS was achieved by NIR irradiation, resulting in simultaneous photothermal and chemotherapeutic actions, yielding superior tumor growth inhibition than those obtained from either type of monotherapy for overcoming drug resistance in cancers.

中文翻译：

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金纳米星的近红外可裂解药物加合物用于克服多重耐药肿瘤。


一种适配体缀合的金纳米星 (dsDDA-AuNS) 已被开发用于靶向肿瘤细胞和肿瘤脉管系统中存在的核仁素，以进行耐药癌症治疗。 AuNS 在近红外 (NIR) 区域具有强吸收性，与一层抗核仁素适体 AS1411 组装在一起。一种抗癌药物，即阿霉素 (DOX)，采用热和酸不稳定的亚甲基键特异性结合在脱氧鸟苷残基上。为了响应近红外辐射，dsDDA-AuNS 允许按需治疗。 AS1411在药物载体-细胞核相互作用中发挥积极作用，增强药物在耐药乳腺癌细胞细胞核中的积累。与裸药相比，静脉注射 dsDDA-AuNS 可以在耐药肿瘤中实现更高的药物积累，即使在等效药物剂量低 54 倍的情况下，也能产生更高的治疗效果。通过近红外辐射实现体内触发的 dsDDA-AuNS 释放 DOX，从而同时产生光热和化疗作用，与任何一种单一疗法相比，在克服癌症耐药性方面产生了更好的肿瘤生长抑制作用。