Cargando…
Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy
Tumor targeting delivery of chemotherapeutic drugs by nanocarriers has been demonstrated to be a promising strategy for cancer therapy with improved therapeutic efficacy. In this work, we reported a novel type of active targeting micelle with pH-responsive drug release by using biodegradable poly(la...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063029/ https://www.ncbi.nlm.nih.gov/pubmed/35520220 http://dx.doi.org/10.1039/c9ra00834a |
_version_ | 1784699079701299200 |
---|---|
author | Chen, Yang Yang, Cejun Mao, Juan Li, Haigang Ding, Jinsong Zhou, Wenhu |
author_facet | Chen, Yang Yang, Cejun Mao, Juan Li, Haigang Ding, Jinsong Zhou, Wenhu |
author_sort | Chen, Yang |
collection | PubMed |
description | Tumor targeting delivery of chemotherapeutic drugs by nanocarriers has been demonstrated to be a promising strategy for cancer therapy with improved therapeutic efficacy. In this work, we reported a novel type of active targeting micelle with pH-responsive drug release by using biodegradable poly(lactide)-poly(2-ethyl-2-oxazoline) di-block copolymers functionalized with spermine (SPM). SPM has been considered as a tumor binding ligand through its specific interaction with the polyamine transport system (PTS), a transmembrane protein overexpressed on various types of cancer cell, while its application in nano-drug delivery systems has rarely been explored. The micelles with spherical shape (∼110 nm) could load hydrophobic paclitaxel (PTX) with high capacity, and release the payload much faster at acidic pH (4.5–6.5) than at pH 7.4. This pH-responsive property assisted the rapid escape of drug from the endo/lysosome after internalization as demonstrated by confocal laser scanning microscopy images using coumarin-6 (Cou-6) as a fluorescent probe. With surface SPM modification, the micelles displayed much higher cellular uptake than SPM lacking micelles in various types of cancer cells, demonstrating tumor targeting ability. The uptake mechanism of SPM modified micelles was explored by flow cytometry, which suggested an energy-consuming sag vesicle-mediated endocytosis pathway. As expected, the micelles displayed significantly enhanced anti-cancer activity. This work demonstrates that SPM modified pH-sensitive micelles may be potential drug delivery vehicles for targeting and effective cancer therapy. |
format | Online Article Text |
id | pubmed-9063029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90630292022-05-04 Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy Chen, Yang Yang, Cejun Mao, Juan Li, Haigang Ding, Jinsong Zhou, Wenhu RSC Adv Chemistry Tumor targeting delivery of chemotherapeutic drugs by nanocarriers has been demonstrated to be a promising strategy for cancer therapy with improved therapeutic efficacy. In this work, we reported a novel type of active targeting micelle with pH-responsive drug release by using biodegradable poly(lactide)-poly(2-ethyl-2-oxazoline) di-block copolymers functionalized with spermine (SPM). SPM has been considered as a tumor binding ligand through its specific interaction with the polyamine transport system (PTS), a transmembrane protein overexpressed on various types of cancer cell, while its application in nano-drug delivery systems has rarely been explored. The micelles with spherical shape (∼110 nm) could load hydrophobic paclitaxel (PTX) with high capacity, and release the payload much faster at acidic pH (4.5–6.5) than at pH 7.4. This pH-responsive property assisted the rapid escape of drug from the endo/lysosome after internalization as demonstrated by confocal laser scanning microscopy images using coumarin-6 (Cou-6) as a fluorescent probe. With surface SPM modification, the micelles displayed much higher cellular uptake than SPM lacking micelles in various types of cancer cells, demonstrating tumor targeting ability. The uptake mechanism of SPM modified micelles was explored by flow cytometry, which suggested an energy-consuming sag vesicle-mediated endocytosis pathway. As expected, the micelles displayed significantly enhanced anti-cancer activity. This work demonstrates that SPM modified pH-sensitive micelles may be potential drug delivery vehicles for targeting and effective cancer therapy. The Royal Society of Chemistry 2019-04-09 /pmc/articles/PMC9063029/ /pubmed/35520220 http://dx.doi.org/10.1039/c9ra00834a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Chen, Yang Yang, Cejun Mao, Juan Li, Haigang Ding, Jinsong Zhou, Wenhu Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title | Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title_full | Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title_fullStr | Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title_full_unstemmed | Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title_short | Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy |
title_sort | spermine modified polymeric micelles with ph-sensitive drug release for targeted and enhanced antitumor therapy |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063029/ https://www.ncbi.nlm.nih.gov/pubmed/35520220 http://dx.doi.org/10.1039/c9ra00834a |
work_keys_str_mv | AT chenyang sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy AT yangcejun sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy AT maojuan sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy AT lihaigang sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy AT dingjinsong sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy AT zhouwenhu sperminemodifiedpolymericmicelleswithphsensitivedrugreleasefortargetedandenhancedantitumortherapy |