Journal
POLYMERS
Volume 8, Issue 11, Pages -Publisher
MDPI AG
DOI: 10.3390/polym8110397
Keywords
co-delivery; pH-responsive; unimolecular micelles; immunotherapy
Categories
Funding
- National Natural Science Foundation of China [91434125]
- Natural Science Foundation of Guangdong Province, China [S2011030001366]
- Science and Technology Foundation of Guangdong Province [2015B020237008]
- University of Minnesota
- China Scholarship Council (CSC) [201406150021]
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Dual functional unimolecular micelles based on a pH-responsive amphiphilic star polymer -CD-(PLA-b-PDMAEMA-b-PEtOxMA)(21) have been developed for the co-delivery of imiquimod and plasmid DNA to dendritic cells. The star polymer with well-defined triblock arms was synthesized by combining activator regenerated by electron-transfer atom-transfer radical polymerization with ring-opening polymerization. Dissipative particle dynamics simulation showed that core-mesophere-shell-type unimolecular micelles could be formed. Imiquimod-loaded micelles had a drug loading of 1.6 wt % and a larger average size (28 nm) than blank micelles (19 nm). The release of imiquimod in vitro was accelerated at the mildly acidic endolysosomal pH (5.0) in comparison to physiologic pH (7.4). Compared with blank micelles, a higher N:P ratio was required for imiquimod-loaded micelles to fully condense DNA into micelleplexes averaging 200-400 nm in size. In comparison to blank micelleplexes, imiquimod-loaded micelleplexes of the same N:P ratio displayed similar or slightly higher efficiency of gene transfection in a mouse dendritic cell line (DC2.4) without cytotoxicity. These results suggest that such pH-responsive unimolecular micelles formed by the well-defined amphiphilic star polymer may serve as promising nano-scale carriers for combined delivery of hydrophobic immunostimulatory drugs (such as imiquimod) and plasmid DNA with potential application in gene-based immunotherapy.
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