Yuan Gangqiang, Luo Xiaoxi, He Kui, Tan Yue, Luo Caiming, Liu Ben, Sun Yidan, Liu Jinbin
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China.
Sci Adv. 2025 Apr 25;11(17):eadw7032. doi: 10.1126/sciadv.adw7032. Epub 2025 Apr 23.
Noninvasive photothermal therapy (PTT) for cancer with photothermal agents (PTAs) has recently achieved success in both preclinical and clinical trials. However, traditional PTAs tend to nonspecifically accumulate in normal liver tissue, hampering their use in PTT of liver tumors. By taking advantage of extremely low liver accumulation from ultrasmall renal-clearable gold nanoparticles (AuNPs), we report a biosafe therapeutic PTT strategy to treat liver tumors precisely through the intratumoral self-assembly of renal-clearable AuNPs at the tumor site via host-guest interactions. After active tumor targeting from the host AuNPs functionalized with both cyclo (Arg-Gly-Asp-d-Phe-Cys) and cyclodextrin, the guest AuNPs functionalized with both pH-responsive doxorubicin and adamantane are designed to precisely trigger intratumoral self-assembly, enhancing both PTT and chemotherapy toward the liver tumor microenvironment. This smart design principle generates a precise therapeutic action toward liver tumors without causing any noticeable heating effect or damage to the surrounding normal liver tissue.
使用光热剂（PTA）进行癌症的非侵入性光热疗法（PTT）最近在临床前和临床试验中均取得了成功。然而，传统的PTA往往会非特异性地积聚在正常肝组织中，这阻碍了它们在肝肿瘤PTT中的应用。通过利用超小肾可清除金纳米颗粒（AuNP）极低的肝脏积聚特性，我们报告了一种生物安全的治疗性PTT策略，该策略通过主客体相互作用在肿瘤部位使肾可清除AuNP在肿瘤内自组装，从而精确治疗肝肿瘤。在用环（精氨酸-甘氨酸-天冬氨酸-d-苯丙氨酸-半胱氨酸）和环糊精功能化的主体AuNP实现主动肿瘤靶向之后，设计用pH响应性阿霉素和金刚烷功能化的客体AuNP以精确触发肿瘤内自组装，增强对肝肿瘤微环境的PTT和化疗效果。这种巧妙的设计原理对肝肿瘤产生精确的治疗作用，而不会对周围正常肝组织造成任何明显的热效应或损伤。
