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.

Graphical abstract

Keywords::

• all-trans retinoic acid
• anti-PD-L1 antibody
• CD8⁺ T cell
• drug delivery
• immuno-treatment
• nanomedicine
• oral dysplasia
• oral squamous cell carcinoma
• poly(lactide-co-glycolide acid)
• PEG

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2019-0397

Author contributions

XJ Chen designed the experiment and drafted the manuscript. XJ Chen and MX Tang performed the experiment. XQ Zhang and G Zhou helped with the manuscript editing. XQ Zhang, Q Liu and G Zhou reviewed the manuscript drafts. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by grants from National Natural Science Foundation of China (no. 81771080, 81970949 and 81371147) to Z Gang. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. Blinded for review: this study was approved by the Ethical Committee Broad of School and Hospital of Stomatology, Wuhan University (no. S07918100E; Wuhan, China), and all efforts were made to minimize suffering of the animals.

Acknowledgments

The authors thank X Wang and M-J He for their help with intravenous injection of tumor-bearing mice.

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China (no. 81771080, 81970949 and 81371147) to Z Gang. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.