Dendritic cell-targeted tumor antigen delivery by glucosylated lipid nanoparticles for precision tumor immunotherapy.

Vaccination is an important approach for cancer immunotherapy, but is limited by the inefficient delivery of immunogenic antigens to dendritic cells (DCs) to stimulate tumor-specific immune responses. Herein, we engineered glucosylated lipid nanoparticles (GluLNPs) to deliver tumor antigens and form personalized vaccines in situ, efficiently targeting DCs to stimulate robust antitumor immunity for the immunotherapy of low-immunogenic breast cancer. Through intratumoral injection, GluLNPs can efficiently capture and deliver tumor antigens, including neoantigens released from eradicated primary triple-negative breast tumors after mild phototherapy with photosensitizer-loaded nanoparticles (i.e., ICGNPs), to DCs, thereby triggering DC maturation and robust antitumor immune responses. Moreover, GluLNPs can effectively elicit strong systemic antitumor immunity against distant and metastatic triple-negative breast tumors when combined with immune checkpoint blockade. This study presents a practical strategy for developing effective DC-targeting personalized nanovaccines and in situ vaccination for precise and effective tumor immunotherapy.