Anti-PD-L1-Modified and ATRA-Loaded Nanoparticles for Immuno-Treatment of Oral Dysplasia and Oral Squamous Cell Carcinoma

Abstract

Aim: To develop nanomedicines for immuno-therapy of oral dysplasia and oral squamous cell carcinoma. Materials & methods: All-trans retinoic acid (ATRA)-poly(lactide-co-glycolide acid) (PLGA)-poly(ethylene glycol) (PEG)-programmed death-ligand 1 (PD-L1) nanomedicines were fabricated by loading ATRA into PLGA-PEG nanocarriers and modification using an anti-PD-L1 antibody. Results: ATRA-PLGA-PEG-PD-L1 nanoparticles showed fast cellular uptake, significantly inhibited proliferation and induced apoptosis in DOK and CAL27 cells. Moreover, in C3H tumor-bearing mice, ATRA-PLGA-PEG-PD-L1 nanoparticles more specifically targeted tumor cells, enhanced anticancer activity and reduced side effects when compared with free ATRA. Furthermore, CD8+ T cells were activated around PD-L1 positive cells in the tumor microenvironment after treatment. Conclusion: ATRA-PLGA-PEG-PD-L1 nanoparticles had low toxicity, high biocompatibility and specifically targeted oral dysplasia and squamous carcinoma cells both in vitro and in vivo.