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

• Published in: Nanoscale Vol. 12; no. 36; pp. 18885 - 18898
• Main Authors: Lan, Xinmiao, Zhu, Wangyong, Huang, Xinshuo, Yu, Yingjie, Xiao, Haihua, Jin, Lijian, Pu, Jingya Jane, Xie, Xi, She, Juncong, Lui, Vivian Wai Yan, Chen, Hui-Jiuan, Su, Yu-xiong
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.09.2020
• Subjects: Animals; Antigens; Apoptosis; Biocompatibility; Cancer therapies; Cell death; Cisplatin; Epidermis; Immune system; Immunotherapy; In vivo methods and tests; Lipids; Mice; Mice, Inbred C57BL; Nanoparticles; Needles; Neoplasms - drug therapy; Robustness (mathematics); Toxicity; Tumor Microenvironment; Tumors
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/d0nr04213g

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. The synergistic effects of immuno-chemotherapy delivered through a microneedle. aPD-1 blocks the binding of PD-L1 to PD-1, leading to the activation of T-cells. Intracellular release of CDDP induces direct cytotoxicity to the tumor cells.