Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 2, Issue 25, Pages 4034-4044Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4tb00439f
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [51103183]
- Guangdong Natural Science Foundation [S2011040001777]
- Doctoral Fund of Ministry of Education of China [20110171120004]
- Project of Zhu Jiang Science and Technology New Star [2012J2200053]
- Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province [2011A060901013]
- Yale University [1044076]
- Fundamental Research Funds for the Central Universities
Ask authors/readers for more resources
Nanosized micelles based on cationic, amphiphilic poly(ethylene glycol)- poly(omega-pentadecalactone-co-Nmethyldiethyleneamine- co-sebacate) (PEG-PPMS) block copolymers have been successfully developed to serve as a new type of biodegradable non-viral vectors for DNA delivery. PEG-PPMS copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of omega-pentadecalactone (PDL), N-methyldiethanolamine (MDEA) and diethyl sebacate (DES) with poly(ethylene glycol) methyl ether (MeO-PEG-OH). The effects of PEG molecular weight, PEG and PDL contents on the biological properties ( including the gene transfection efficiency) of the copolymer micelles were investigated. The LucDNA-loaded micelles formed from the copolymers with 30-50 wt% PEG showed high stability in serum-containing aqueous medium, which is in sharp contrast to rapid aggregation of LucDNA/PPMS polyplex particles. The conjugation of PEG to PPMS chains significantly reduces the cytotoxicity and hemolysis activity of the PEG-PPMS micelles. Compared to PEG-free PPMS, the micelles of PEG-PPMS copolymers with optimal compositions (e.g., 42% PEG5K-PPMS-10% PDL and 42% PEG5K-PPMS-20% PDL) exhibited enhanced capability to condense and protect DNA. Although the optimized micelles showed comparable or slightly lower gene transfection efficacy than the reference PPMS in vitro, the efficiency of LucDNA/42% PEG5K-PPMS-20% PDL micelles in transfecting tumor cells in mice was twice as high as that of LucDNA/PPMS polyplex particles due to their strong DNA condensation ability and excellent stability under physiological conditions. The PEG- PPMS micelle system with improved properties is a family of potentially promising non-viral vectors for in vivo delivery of therapeutic genes to treat tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available