ER-Targeting PDT Converts Tumors into In Situ Therapeutic Tumor Vaccines

A therapeutic tumor vaccine is a promising approach to cancer treatment. One of its strategies is to treat patient-derived tumor cells in vitro and then administer them in vivo to induce an adaptive immune response and achieve cancer treatment. Here, we want to explore the possibility of converting cancer tissue into a therapeutic tumor vaccine through induced immunogenic cell death (ICD) in situ. We loaded indocyanine green (ICG) into liposomes (ICG-Lipo) and modified it with the pardaxin peptide to realize an endoplasmic reticulum (ER)-targeting function (Par-ICG-Lipo). A microfluidic technique was developed for loading ICG, a water-soluble molecule, into liposomes with a high encapsulation efficiency (greater than 90%). Under near-infrared (NIR) irradiation, ER-targeting photodynamic therapy (PDT) induced by Par-ICG-Lipo could promote the release of danger-signaling molecules (DAMPs) and tumor antigens (TAAs) in vivo, which significantly enhanced the immunogenicity in vivo and thus stimulates a strong antitumor immune response. This process would be further amplified by adopting dendritic cells. In general, our strategy transformed in situ tumor cells into therapeutic vaccines by ER-targeting PDT, which could provide a clinically applicable and effective approach for cancer treatment.