Ag nanoparticles enhance immune checkpoint blockade efficacy by promoting of immune surveillance in melanoma.

Abstract

Immune checkpoint blockade (ICB) therapy, represented by programmed cell death protein 1 (PD-1) and its ligand (PD-L1) monoclonal antibodies (mAbs), has shown an obvious benefit for melanoma immunotherapy, but the overall response rate is still low. To find an effective combination therapy strategy, we successfully produced small size silver nanoparticles coated with sucrose (S-AgNPs) as potent adjuvants. The antitumor effects of S-AgNPs were tested in vitro and comparatively investigated in immunodeficient and immunocompetent mice with melanoma. Fluorescence-activated cell sorting and immunofluorescent staining analysis were conducted to identify the tumor microenvironments. The expression of PD-L1 in tumors was tested by multiple methods. The combination therapy and potential toxicity of S-AgNPs and PD-1 mAbs were assessed in melanoma-bearing mice. In our findings, S-AgNPs presented potent antitumor effects, good druggability and low systemic toxicity. Functionally, we found that S-AgNPs exhibited better antitumor effects in immunocompetent mice. Mechanistically, we showed that S-AgNPs suppress tumor cell proliferation by inducing cellular apoptosis and promote cytotoxic CD8+ T cell infiltration and activity. Preclinically, S-AgNPs showed excellent local antitumor activity and mild systemic immunotoxicity with PD-1 mAbs in the inhibition of melanoma proliferation, providing a novel clinical combination treatment strategy.

• Authors: Xinwei Kuang, Zhenxing Wang, Zhongwei Luo, Zehui He, Long Liang, Qian Gao, Youyou Li, Kun Xia, Zuozhong Xie, Ruimin Chang, Yiyi Wang, Yiwei Liu, Shuang Zhao, Juan Su, Yang Wang, Weiyi Situ, Mingliang Chen, Yuetao Zhao, Xiang Chen, Hui Xie, Hong Liu
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 616 Pg. 189-200 (Jun 15 2022) ISSN: 1095-7103 [Electronic] United States
• PMID: 35203032 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• B7-H1 Antigen
• Immune Checkpoint Inhibitors
• Programmed Cell Death 1 Receptor
• Silver

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• B7-H1 Antigen (metabolism)
• Cell Line, Tumor
• Immune Checkpoint Inhibitors
• Melanoma (drug therapy, pathology)
• Metal Nanoparticles
• Mice
• Programmed Cell Death 1 Receptor (metabolism)
• Silver (pharmacology)
• Tumor Microenvironment