Cargando…
Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release
To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX) were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid) (poly(γ-GA)), f...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961315/ https://www.ncbi.nlm.nih.gov/pubmed/24651156 http://dx.doi.org/10.1371/journal.pone.0092268 |
_version_ | 1782308276247986176 |
---|---|
author | Chiang, Wen-Hsuan Huang, Wen-Chia Shen, Ming-Yin Wang, Che-Hsu Huang, Yi-Fong Lin, Sung-Chyr Chern, Chorng-Shyan Chiu, Hsin-Cheng |
author_facet | Chiang, Wen-Hsuan Huang, Wen-Chia Shen, Ming-Yin Wang, Che-Hsu Huang, Yi-Fong Lin, Sung-Chyr Chern, Chorng-Shyan Chiu, Hsin-Cheng |
author_sort | Chiang, Wen-Hsuan |
collection | PubMed |
description | To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX) were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid) (poly(γ-GA)), followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide)-g-monomethoxy poly(ethylene glycol) in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs) showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37°C) at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment. |
format | Online Article Text |
id | pubmed-3961315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39613152014-03-27 Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release Chiang, Wen-Hsuan Huang, Wen-Chia Shen, Ming-Yin Wang, Che-Hsu Huang, Yi-Fong Lin, Sung-Chyr Chern, Chorng-Shyan Chiu, Hsin-Cheng PLoS One Research Article To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX) were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid) (poly(γ-GA)), followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide)-g-monomethoxy poly(ethylene glycol) in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs) showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37°C) at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment. Public Library of Science 2014-03-20 /pmc/articles/PMC3961315/ /pubmed/24651156 http://dx.doi.org/10.1371/journal.pone.0092268 Text en © 2014 Chiang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chiang, Wen-Hsuan Huang, Wen-Chia Shen, Ming-Yin Wang, Che-Hsu Huang, Yi-Fong Lin, Sung-Chyr Chern, Chorng-Shyan Chiu, Hsin-Cheng Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title | Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title_full | Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title_fullStr | Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title_full_unstemmed | Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title_short | Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release |
title_sort | dual-layered nanogel-coated hollow lipid/polypeptide conjugate assemblies for potential ph-triggered intracellular drug release |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961315/ https://www.ncbi.nlm.nih.gov/pubmed/24651156 http://dx.doi.org/10.1371/journal.pone.0092268 |
work_keys_str_mv | AT chiangwenhsuan duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT huangwenchia duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT shenmingyin duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT wangchehsu duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT huangyifong duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT linsungchyr duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT chernchorngshyan duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease AT chiuhsincheng duallayerednanogelcoatedhollowlipidpolypeptideconjugateassembliesforpotentialphtriggeredintracellulardrugrelease |