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Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430442/ https://www.ncbi.nlm.nih.gov/pubmed/22977303 http://dx.doi.org/10.2147/IJN.S34675 |
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author | Li, Wei Li, Huafei Li, Jinfeng Wang, Huajing Zhao, He Zhang, Li Xia, Yu Ye, Zengwei Gao, Jie Dai, Jianxin Wang, Hao Guo, Yajun |
author_facet | Li, Wei Li, Huafei Li, Jinfeng Wang, Huajing Zhao, He Zhang, Li Xia, Yu Ye, Zengwei Gao, Jie Dai, Jianxin Wang, Hao Guo, Yajun |
author_sort | Li, Wei |
collection | PubMed |
description | The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional “gold-standard” polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS(®) Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy. |
format | Online Article Text |
id | pubmed-3430442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34304422012-09-13 Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors Li, Wei Li, Huafei Li, Jinfeng Wang, Huajing Zhao, He Zhang, Li Xia, Yu Ye, Zengwei Gao, Jie Dai, Jianxin Wang, Hao Guo, Yajun Int J Nanomedicine Original Research The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional “gold-standard” polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS(®) Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy. Dove Medical Press 2012 2012-08-22 /pmc/articles/PMC3430442/ /pubmed/22977303 http://dx.doi.org/10.2147/IJN.S34675 Text en © 2012 Li et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Li, Wei Li, Huafei Li, Jinfeng Wang, Huajing Zhao, He Zhang, Li Xia, Yu Ye, Zengwei Gao, Jie Dai, Jianxin Wang, Hao Guo, Yajun Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title | Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title_full | Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title_fullStr | Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title_full_unstemmed | Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title_short | Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
title_sort | self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430442/ https://www.ncbi.nlm.nih.gov/pubmed/22977303 http://dx.doi.org/10.2147/IJN.S34675 |
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