Journal
BIOMATERIALS
Volume 34, Issue 21, Pages 5391-5401Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.03.083
Keywords
Gene delivery; Cationic polymer; Non-viral vector; Ring-opening polymerization; Structure-activity relationships
Funding
- National Program on Key Basic Research Project of China (973 Program) [2012CB720603]
- National Science Foundation of China [21232005]
- State Key Lab of Oral Diseases (Sichuan University) [SKLODSCUKF2012-02]
- Program for New Century Excellent Talents in University [NCET-11-0354]
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For a clinically effective non-viral gene delivery system, a non-toxic and highly efficient vector is of great importance. A series of linear cationic polymers were synthesized by the ring-opening polymerization between diglycidyl ethers and diamines. Their structure activity relationships as gene delivery vectors were systematically studied. Besides the amino groups with various densities, these polymers have uniform distribution of hydroxyl groups, which were formed in the polymerization and may benefit their biocompatibility and serum-tolerance. These polymers have good DNA binding ability and could condense DNA into nanoparticles with proper sizes and zeta-potentials. MIT assay revealed that polyplexes formed from title polymers have lower cytotoxicity than that derived from PEI. Most of the polymers have higher transfection efficiency than 25 kDa PEI in the in vitro transfection experiments. Polymers prepared from diglycidyl ethers with less or no N atom (2a and 2b) gave dramatically decreased TE, indicating that secondary amine on the backbone is highly required for efficient gene transfection, and compound 2 may be a good building block in the design of cationic polymers for gene delivery. More importantly, these polymers showed much better serum tolerance. Unlike PEI, the transfection mediated by P5 was seldom affected by the presence of 10% serum. Cellular uptake and intracellular distribution studies also confirmed the good performance of P5 in the transfection process with serum. (C) 2013 Elsevier Ltd. All rights reserved.
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