Microneedles loaded with anti-PD-1-cisplatin nanoparticles for synergistic cancer immuno-chemotherapy.

Abstract

Programmed cell death protein-1 (PD-1) on T-cells combined with programmed cell death ligand-1 (PD-L1) critically accounts for tumor immune evasion. Anti-PD-1 (aPD-1) blocks the binding of PD-1 to PD-L1, thus allowing T-cell activation for tumor cell eradication. Currently, the major challenges for cancer immunotherapy are how to improve the response rate and overcome drug resistance. Dermal administration turns out to be a promising route for immunotherapy since skin is a highly active immune organ containing a large population of resident antigen-presenting cells. Microneedle arrays can pierce the immune-cell-rich epidermis, leading to a robust T-cell response in the microenvironment of tumor cells. Herein, we successfully developed a microneedle patch loaded with pH-responsive tumor-targeted lipid nanoparticles (NPs), which allows local delivery of aPD-1 and cisplatin (CDDP) precisely to cancer tissues for cancer therapy. For in vivo studies, aPD-1/CDDP@NPs delivered through microneedles effectively boosted the immune response, thereby a remarkable effect on tumor regression was realized. Synergistic anticancer mechanisms were therefore activated through robust microneedle-induced T-cell response, blockage of PD-1 in T-cells by aPD-1, and an increase in direct cytotoxicity of CDDP in tumor cells. Strikingly, transdermal delivery using MNs increased the response rate in the animal model unresponsive to aPD-1 systemic therapy. This exhibited promise in the treatment of immunotherapy-unresponsive cancers. Taken together, microneedle-mediated local delivery of nano-encapsulated chemotherapeutic and immunotherapeutic agents at tumor skin sites provides a novel treatment strategy and insights into cancer therapy.

• Authors: Xinmiao Lan , Wangyong Zhu , Xinshuo Huang , Yingjie Yu , Haihua Xiao , Lijian Jin , Jingya Jane Pu , Xi Xie , Juncong She , Vivian Wai Yan Lui , Hui-Jiuan Chen , Yu-Xiong Su
• Journal: Nanoscale (Nanoscale) Vol. 12 Issue 36 Pg. 18885-18898 (Sep 28 2020) ISSN: 2040-3372 [Electronic] England
• PMID: 32902555 (Publication Type: Journal Article)

Chemical References

• Cisplatin

Topics

• Animals
• Cisplatin
• Immunotherapy
• Mice
• Mice, Inbred C57BL
• Nanoparticles
• Neoplasms (drug therapy)
• Tumor Microenvironment