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Article: Microneedles loaded with anti-PD-1–cisplatin nanoparticles for synergistic cancer immuno-chemotherapy
Title | Microneedles loaded with anti-PD-1–cisplatin nanoparticles for synergistic cancer immuno-chemotherapy |
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Authors | |
Issue Date | 2020 |
Publisher | RSC Publications. The Journal's web site is located at http://pubs.rsc.org/en/journals/journalissues/nr#!recentarticles&all |
Citation | Nanoscale, 2020, v. 12 n. 36, p. 18885-18898 How to Cite? |
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. Forin vivostudies, 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. |
Description | Hybrid open access |
Persistent Identifier | http://hdl.handle.net/10722/297274 |
ISSN | 2023 Impact Factor: 5.8 2023 SCImago Journal Rankings: 1.416 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | LAN, X | - |
dc.contributor.author | ZHU, W | - |
dc.contributor.author | Huang, X | - |
dc.contributor.author | Yu, Y | - |
dc.contributor.author | Xiao, H | - |
dc.contributor.author | Jin, L | - |
dc.contributor.author | Pu, JJ | - |
dc.contributor.author | Xie, X | - |
dc.contributor.author | She, J | - |
dc.contributor.author | Lui, VWY | - |
dc.contributor.author | Chen, HJ | - |
dc.contributor.author | Su, YX | - |
dc.date.accessioned | 2021-03-08T07:16:38Z | - |
dc.date.available | 2021-03-08T07:16:38Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Nanoscale, 2020, v. 12 n. 36, p. 18885-18898 | - |
dc.identifier.issn | 2040-3364 | - |
dc.identifier.uri | http://hdl.handle.net/10722/297274 | - |
dc.description | Hybrid open access | - |
dc.description.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. Forin vivostudies, 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. | - |
dc.language | eng | - |
dc.publisher | RSC Publications. The Journal's web site is located at http://pubs.rsc.org/en/journals/journalissues/nr#!recentarticles&all | - |
dc.relation.ispartof | Nanoscale | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Microneedles loaded with anti-PD-1–cisplatin nanoparticles for synergistic cancer immuno-chemotherapy | - |
dc.type | Article | - |
dc.identifier.email | Jin, L: ljjin@hkucc.hku.hk | - |
dc.identifier.authority | Jin, L=rp00028 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1039/D0NR04213G | - |
dc.identifier.pmid | 32902555 | - |
dc.identifier.scopus | eid_2-s2.0-85091629819 | - |
dc.identifier.hkuros | 321503 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 36 | - |
dc.identifier.spage | 18885 | - |
dc.identifier.epage | 18898 | - |
dc.identifier.isi | WOS:000572677500034 | - |
dc.publisher.place | United Kingdom | - |