Aptamer- and Lauric Acid-Modified Au Nanocrystals for Targeted Doxorubicin Delivery and Combined Phototherapy, Chemotherapy, and Immunotherapy

A bispecific thermosensitive system was created to deliver drugs and aid T cells in identifying cancer cells for enhancing the tumor-killing effect. Among various nanocarriers, gold nanocages (AuNCs) were selected as the photothermal agents for photothermal therapy (PTT) due to their distinctive hollow and void structures, which make them ideal carriers throughout the therapy. To achieve controlled drug release under near-infrared radiation, lauric acid (LA) was chosen as the "gatekeeper", responding to a temperature stimulus. Bispecific aptamers with surface modifications were utilized to increase the intracellular drug content while triggering the immune system to eliminate the cancer cells. The homologous targeting ability of AuNCs/LA/ doxorubicin (DOX)/Apt resulted in a high tumor site aggregation. PTT-induced in situ tumor heat elimination and increased tumor cell immunogenicity upon exposure to laser irradiation. Consequently, the smart nano platform not only destroyed the tumor cells through PTT and chemotherapy but also formed a T cell–cancer cell complex at the tumor site, causing the immune cells to precisely identify the tumor and achieve in situ activation of the immune response at the tumor site. The proposed strategy was a classic "cocktail therapy".