期刊
ACS NANO
卷 5, 期 5, 页码 3493-3505出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn102540y
关键词
nanocarrier; siRNA delivery; in vitro performance; in vivo biodistribution; polyplex; micelleplex
类别
资金
- National Science Foundation [CBET-0828574, DMR-0906567]
- Showalter Trust
- Purdue Research Foundation
- IUSM/CTR
- NIH/NCRR [RR025761]
- NIH [R01CA124586]
- GEM Consortium
Micelle-based siRNA carriers (micelleplexes) were prepared from the A B C triblock copolymer poly(ethylene glycol)-poly(n-butyl acrylate)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PnBA-PDMAEMA), and their in Vitro performance and in vivo biodistribution properties were compared with the benchmark PEGylated and basic polycation systems PEG-PDMAEMA and PDMAEMA, respectively. The micelle architecture,, incorporating increased PEG shielding and a larger particle size (similar to 50 nm) than polycation-based complexes (polyplexes; similar to 10 nm), enhances siRNA delivery performance In two Important aspects: in vitro gene silencing efficiency and In vivo tumor accumulation. The In vitro gene silencing efficiency of the micelleplexes (24% in Beta cells) was significantly better than the statistically insignificant levels observed for PDMAEMA and PEG-PDMAEMA polyplexes under identical conditions. This enhancement is linked to the different mechanisms by which micelleplexes are internalized (i.e., caveolar, etc.) compared to PDMAEMA and PEG-PDMAEMA polyplexes. Folate-functionalization significantly improved micelleplex uptake but had negligible influence on gene-silencing efficiency, suggesting that this parameter is not limited by cellular internalization. In vivo biodistribution analysis revealed that siRNA delivered by micelleplexes was more effectively accumulated and retained in tumor tissues than that delivered by PEGylated polyplexes. Overall, the micelle particle size and architecture appear to improve in vitro and in vivo delivery characteristics without significantly changing other properties, such as cytotoxicity and resistance to enzymes and dissociation. The self-assembled nature of micelleplexes is expected to enable Incorporation of imaging modalities Inside the hydrophobic micelle core, thus combining therapeutic and diagnostic capabilities. The findings from the present study suggest that the micelleplex-type carrier architecture is a useful platform for potential theranostic and tumor-targeting applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据