Chemo-immunotherapy has shown great promise as a next-generation treatment strategy for established solid tumors. Cheng et al. first developed the PD-L1- and CD44-responsive multifunctional nanoparticles (MNPs) utilizing a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). PEI-OA increases the drug loading capacity and encapsulation efficiency of the nanoplatform. Anti-PD-L1 antibody promotes its cellular uptake, increases the levels of CD4+ and CD8+ T cells and inhibits primary breast cancer at the tumor site. Paclitaxel triggers tumor cells apoptosis directly, and then produces tumor vaccines to promote the dendritic cells (DCs) maturation, finally primes the T cells activation. Ovalbumin as a model antigen and CpG as an immunopotentiator to stimulate the DCs maturation. Moreover, chloroquine turns the “immune-cold” environment and potentiates the anti-tumor effect of both immune checkpoint inhibitor and chemotherapeutics, thus synergically and efficiently improving the breast cancer immunotherapy.

Anti-PD-L1 antibody, Autophagy response, Immuno-chemotherapy, Multifunctional nanoparticles