Antitumor and Immunotherapy Sensitizing Effects of a Thermosensitive Liposome by Increasing Autophagosome Accumulation

In the past decade, tumor treatment strategies have shifted from tumors to the immune system of tumor patients. NIR laser-induced photothermal therapy can not only generate heat or reactive oxygen species to kill tumors but also induce immunogenic cell death and activate the overall antitumor immune response. The ICD process is usually accompanied by autophagosome formation, which contains tumor-associated antigens. However, the fusion of autophagosome and lysosome impairs antigens, weakening the antitumor immune response. Thus, administration with autophagy terminal inhibitors could be a compensatory strategy. In this work, we prepared a thermally sensitive liposome drug delivery system containing the photothermal agent IR780 and autophagy inhibitor HCQ (IR780/HCQ-Lip). IR780/HCQ-Lip has a uniform particle size distribution and good photodynamic and photothermal properties. The inhibition of autophagy enhanced the phototherapy effect. Compared with the survival rate of 4T1 cells being treated with IR780-Lip phototherapy alone (36.87%), the survival rate of the IR780/HCQ-Lip group decreased to 3.71%. IR780/HCQ-Lip caused a massive accumulation of autophagosomes, promoted the maturation of dendritic cells (DCs), and enhanced the infiltration of intratumoral T cells. In addition, IR780/HCQ-Lip produced a systemic immune response and also showed good inhibition of distal tumor growth under laser action in distal tumor experiments. Thus, IR780/HCQ-Lip exhibited a promising combination therapy for the treatment of breast cancer.