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Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine
The greatest obstacle to clinical application of cancer gene therapy is lack of effective delivery tools. Gene delivery vehicles must protect against degradation, avoid immunogenic effects and prevent off target delivery which can cause harmful side effects. PEGylated liposomes have greatly improved...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675078/ https://www.ncbi.nlm.nih.gov/pubmed/29313012 http://dx.doi.org/10.1002/btm2.10022 |
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author | Levine, Rachel M. Dinh, Christina V. Harris, Michael A. Kokkoli, Efrosini |
author_facet | Levine, Rachel M. Dinh, Christina V. Harris, Michael A. Kokkoli, Efrosini |
author_sort | Levine, Rachel M. |
collection | PubMed |
description | The greatest obstacle to clinical application of cancer gene therapy is lack of effective delivery tools. Gene delivery vehicles must protect against degradation, avoid immunogenic effects and prevent off target delivery which can cause harmful side effects. PEGylated liposomes have greatly improved tumor localization of small molecule drugs and are a promising tool for nucleic acid delivery as the polyethylene glycol (PEG) coating protects against immune recognition and blood clearance. In this study, small interfering RNA (siRNA) was fully encapsulated within PEGylated liposomes by complexing the siRNA with a cationic polymer, polyethyleneimine (PEI), before encapsulation. Formation methods and material compositions were then investigated for their effects on encapsulation. This technology was translated for protective delivery of siRNA designed for human papillomavirus (HPV) viral gene silencing and cervical cancer treatment. PEGylated liposomes encapsulating siRNA were functionalized with the AG86 targeting peptide‐amphiphile which binds to the α(6)β(4) integrin, a cervical cancer biomarker. It was found that both targeting and polymer complexation before encapsulation were critical components to effective transfection. |
format | Online Article Text |
id | pubmed-5675078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56750782018-01-08 Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine Levine, Rachel M. Dinh, Christina V. Harris, Michael A. Kokkoli, Efrosini Bioeng Transl Med Research Reports The greatest obstacle to clinical application of cancer gene therapy is lack of effective delivery tools. Gene delivery vehicles must protect against degradation, avoid immunogenic effects and prevent off target delivery which can cause harmful side effects. PEGylated liposomes have greatly improved tumor localization of small molecule drugs and are a promising tool for nucleic acid delivery as the polyethylene glycol (PEG) coating protects against immune recognition and blood clearance. In this study, small interfering RNA (siRNA) was fully encapsulated within PEGylated liposomes by complexing the siRNA with a cationic polymer, polyethyleneimine (PEI), before encapsulation. Formation methods and material compositions were then investigated for their effects on encapsulation. This technology was translated for protective delivery of siRNA designed for human papillomavirus (HPV) viral gene silencing and cervical cancer treatment. PEGylated liposomes encapsulating siRNA were functionalized with the AG86 targeting peptide‐amphiphile which binds to the α(6)β(4) integrin, a cervical cancer biomarker. It was found that both targeting and polymer complexation before encapsulation were critical components to effective transfection. John Wiley and Sons Inc. 2016-08-08 /pmc/articles/PMC5675078/ /pubmed/29313012 http://dx.doi.org/10.1002/btm2.10022 Text en © 2016 The Authors. Bioengineering & Translational Medicine is published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Reports Levine, Rachel M. Dinh, Christina V. Harris, Michael A. Kokkoli, Efrosini Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title | Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title_full | Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title_fullStr | Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title_full_unstemmed | Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title_short | Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine |
title_sort | targeting hpv‐infected cervical cancer cells with pegylated liposomes encapsulating sirna and the role of sirna complexation with polyethylenimine |
topic | Research Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675078/ https://www.ncbi.nlm.nih.gov/pubmed/29313012 http://dx.doi.org/10.1002/btm2.10022 |
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