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Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention
INTRODUCTION: Oral squamous cell carcinoma (OSCC), is associated with high morbidity and mortality. Preemptive interventions have been postulated to provide superior therapeutic options, but their implementation has been restricted by the availability of broadly applicable local delivery systems. ME...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036282/ https://www.ncbi.nlm.nih.gov/pubmed/36635487 http://dx.doi.org/10.1007/s11095-022-03465-x |
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author | Habibi, Nahal Bissonnette, Caroline Pei, Ping Wang, Daren Chang, Albert Raymond, Jeffery E. Lahann, Joerg Mallery, Susan R. |
author_facet | Habibi, Nahal Bissonnette, Caroline Pei, Ping Wang, Daren Chang, Albert Raymond, Jeffery E. Lahann, Joerg Mallery, Susan R. |
author_sort | Habibi, Nahal |
collection | PubMed |
description | INTRODUCTION: Oral squamous cell carcinoma (OSCC), is associated with high morbidity and mortality. Preemptive interventions have been postulated to provide superior therapeutic options, but their implementation has been restricted by the availability of broadly applicable local delivery systems. METHODS: We address this challenge by engineering a delivery vehicle, Janus nanoparticles (JNP), that combine the dual mucoadhesive properties of a first cationic chitosan compartment with a second hydrophobic poly(lactide-co-glycolide) release compartment. JNP are designed to avoid rapid mucus clearance while ensuring stable loading and controlled release of the IL-6 receptor antagonist, tocilizumab (TCZ). RESULTS: The JNP featured defined and monodispersed sizes with an average diameter of 327 nm and a PDI of 0.245, high circularities above 0.90 and supported controlled release of TCZ and effective internalization by oral keratinocytes. TCZ released from JNP retained its biological activity and effectively reduced both, soluble and membrane-bound IL-6Rα (71% and 50%). In full-thickness oral mucosal explants, 76% of the JNP breached the stratum corneum and in 41% were observed in the basal cell layer indicating excellent mucopenetrating properties. When tested in an aggressive OSCC xenograft model, TCZ-loaded JNP showed high levels of xenograft inhibition and outperformed all control groups with respect to inhibition of tumor cell proliferation, reduction in tumor size and reduced expression of the proto-oncogene ERG. CONCLUSION: By combining critically required, yet orthogonal properties within the same nanoparticle design, the JNP in this study, demonstrate promise as precision delivery platforms for intraoral field-coverage chemoprevention, a vastly under-researched area of high clinical importance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11095-022-03465-x. |
format | Online Article Text |
id | pubmed-10036282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-100362822023-03-25 Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention Habibi, Nahal Bissonnette, Caroline Pei, Ping Wang, Daren Chang, Albert Raymond, Jeffery E. Lahann, Joerg Mallery, Susan R. Pharm Res Original Research Article INTRODUCTION: Oral squamous cell carcinoma (OSCC), is associated with high morbidity and mortality. Preemptive interventions have been postulated to provide superior therapeutic options, but their implementation has been restricted by the availability of broadly applicable local delivery systems. METHODS: We address this challenge by engineering a delivery vehicle, Janus nanoparticles (JNP), that combine the dual mucoadhesive properties of a first cationic chitosan compartment with a second hydrophobic poly(lactide-co-glycolide) release compartment. JNP are designed to avoid rapid mucus clearance while ensuring stable loading and controlled release of the IL-6 receptor antagonist, tocilizumab (TCZ). RESULTS: The JNP featured defined and monodispersed sizes with an average diameter of 327 nm and a PDI of 0.245, high circularities above 0.90 and supported controlled release of TCZ and effective internalization by oral keratinocytes. TCZ released from JNP retained its biological activity and effectively reduced both, soluble and membrane-bound IL-6Rα (71% and 50%). In full-thickness oral mucosal explants, 76% of the JNP breached the stratum corneum and in 41% were observed in the basal cell layer indicating excellent mucopenetrating properties. When tested in an aggressive OSCC xenograft model, TCZ-loaded JNP showed high levels of xenograft inhibition and outperformed all control groups with respect to inhibition of tumor cell proliferation, reduction in tumor size and reduced expression of the proto-oncogene ERG. CONCLUSION: By combining critically required, yet orthogonal properties within the same nanoparticle design, the JNP in this study, demonstrate promise as precision delivery platforms for intraoral field-coverage chemoprevention, a vastly under-researched area of high clinical importance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11095-022-03465-x. Springer US 2023-01-12 2023 /pmc/articles/PMC10036282/ /pubmed/36635487 http://dx.doi.org/10.1007/s11095-022-03465-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Article Habibi, Nahal Bissonnette, Caroline Pei, Ping Wang, Daren Chang, Albert Raymond, Jeffery E. Lahann, Joerg Mallery, Susan R. Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title | Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title_full | Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title_fullStr | Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title_full_unstemmed | Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title_short | Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention |
title_sort | mucopenetrating janus nanoparticles for field-coverage oral cancer chemoprevention |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036282/ https://www.ncbi.nlm.nih.gov/pubmed/36635487 http://dx.doi.org/10.1007/s11095-022-03465-x |
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