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

Abstract

<b>Aim:</b> To develop nanomedicines for immuno-therapy of oral dysplasia and oral squamous cell carcinoma. <b>Materials & methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> ATRA-PLGA-PEG-PD-L1 nanoparticles had low toxicity, high biocompatibility and specifically targeted oral dysplasia and squamous carcinoma cells both <i>in vitro</i> and <i>in vivo</i>.