Microfluidic PLGA microcapsules with PD-L1 aptamers and docetaxel encapsulation for enhancing tumor immunity

Immunotherapy has made encouraging progress in the field of cancer treatment. Among them, the programmed cell death-ligand 1 (PD-L1) antibody-mediated immunotherapy has stimulated the development of various carrier delivery systems. Inspired by related researchs, in this study, we prepare core-shell structured poly(lactide-co-glycolide) (PLGA) microcapsules as a drug delivery system through microfluidics technology, loaded with PD-L1 aptamers and chemotherapy drug docetaxel. The PD-L1 aptamer loaded in the nuclear layer binds to the PD-L1 molecule produced by tumor cells, blocking the immune checkpoint protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. As a result, phagocytosis of tumor cells is promoted by using lipopolysaccharide (LPS) induced tumor associated macrophages. Furthermore, docetaxel in the shell is further released, inhibiting tumor cell growth as the PLGA microcapsules degrade. More importantly, the combination of PD-L1 aptamers and the chemotherapy drug docetaxel improved the immune response of the tumor. It showed significant anti-tumor activity and reduced systemic side effects in the melanoma model. At present, more and more nucleic acid aptamers as affinity reagents that can replace antibodies have been used to improve tumor treatment. Therefore, this therapeutic strategy provides more possibilities for tumor treatment by combining aptamer molecules with chemotherapy drugs when exploring more effective combination drugs.