Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers
| Autor: | David J. Peeler, Yilong Cheng, James Kevin Y Tan, Drew L. Sellers, Suzie H. Pun, Philip J. Horner |
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| Rok vydání: | 2017 |
| Předmět: |
Materials science
Polymers Proton Magnetic Resonance Spectroscopy Biophysics Bioengineering 02 engineering and technology Gene delivery Transfection 010402 general chemistry Methacrylate 01 natural sciences Article Biomaterials chemistry.chemical_compound Nucleic Acids Polymer chemistry Polyamines Animals Humans Luciferases chemistry.chemical_classification Gene Transfer Techniques Cationic polymerization Polymer Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Polyelectrolytes Combinatorial chemistry 0104 chemical sciences Mice Inbred C57BL chemistry Mechanics of Materials Hydrodynamics Ceramics and Composites Nucleic acid Female Amine gas treating 0210 nano-technology Ethylene glycol HeLa Cells |
| Zdroj: | Biomaterials. 127:89-96 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2017.02.036 |
| Popis: | Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)–b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery. |
| Databáze: | OpenAIRE |
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