Thermosensitive liposome-encapsulated gold nanocages for photothermal-modulated drug release and synergistic photothermal therapy

Delivery nanosystems have been widely developed to improve the efficacy of chemotherapy. However, their performance regarding the non-specific leakage of drugs remained unsatisfactory. Herein, gold nanocages (AuNCs) were used as carriers and thermo-sensitive liposome (TSL) as a protective shell to design a camptothecin (CPT)-loaded delivery nanosystem (AuNCs/CPT@TSL) for photothermal-modulated drug release. This approach effectively avoided the non-specific leakage of CPT and enabled the combination of photothermal therapy (PTT) and chemotherapy. In the simulated tumor microenvironment (pH = 5.5), the TSL shell prevented CPT leakage at 37 °C, with a release rate of only 11.4%. However, the release rate of CPT greatly increased to 85.4% when the temperature was elevated to 45 °C. The photothermal conversion efficiency of AuNCs/CPT@TSL reached up to 46.1%. At an incubation temperature of 37 °C, the cell survival rate decreased to 43.6% in AuNCs/CPT but remained above 90% in AuNCs/CPT@TSL, demonstrating the protective effect of the TSL shell. Under the combination of PTT and chemotherapy, cell viability drastically decreased to 10.9%, and the tumors completely disappeared, confirming the safe and reliable antitumor effect of AuNCs/CPT@TSL.