Intratumoral self-assembly of renal-clearable gold nanoparticles as precise photothermal nanomedicine for liver tumor therapy

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.