Photothermal-triggered dendrimer nanovaccines boost systemic antitumor immunity

Tumor vaccine that can effectively activate or strengthen the body's antitumor immune response to kill and eliminate tumor cells has attracted widespread attention. Currently developed tumor vaccines have severe shortcomings such as low bioavailability and lack of dual or multiple functions, resulting in poor antitumor efficacy. Herein, we report the development of an advanced nanosystem integrated with phenylboronic acid (PBA)-functionalized poly(amidoamine) dendrimers of generation 5 (G5), copper sulfide nanoparticles, and cyclic GMP-AMP (cGAMP), an immune adjuvant (for short, G5-PBA@CuS/cGAMP) to act as a photothermal-triggered nanovaccine. We show that the prepared functional nanosystem possesses an average CuS core size of 3.6 nm, prominent near-infrared absorption feature to have an excellent photothermal conversion efficiency of 44.0%, and good protein adsorption characteristics due to the PBA modification. With these features, the developed nanosystem can be adopted for photothermal therapy of primary melanoma tumors and simultaneously absorb the whole tumor cell antigens, thus creating photothermal-triggered dendrimeric nanovaccine of G5-PBA@CuS/cGAMP/antigen in situ to induce antitumor immune response to inhibit the distal tumors as well. Meanwhile, melanoma cells treated with the G5-PBA@CuS in vitro under laser irradiation allowed the creation of G5-PBA@CuS/antigen complexes that could be further integrated with cGAMP to form preformed nanovaccine for effective primary tumor inhibition and tumor occurrence prevention. The designed photothermal-triggered dendrimeric nanovaccine may represent an advanced nanomedicine formulation to effectively inhibit the growth of primary and distal tumors, and prevent tumor occurrence through the stimulated systemic antitumor immunity.