1. Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
- Author
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Xiong Ding, Guangzhao Mao, Lingxiao Xie, and Rachel Budry
- Subjects
polyelectrolyte multilayers ,Biophysics ,Pharmaceutical Science ,Bioengineering ,Biocompatible Materials ,02 engineering and technology ,sequential release ,Gene delivery ,010402 general chemistry ,Microscopy, Atomic Force ,Transfection ,01 natural sciences ,Time-Lapse Imaging ,localized gene delivery ,Biomaterials ,chemistry.chemical_compound ,Mice ,interlayer diffusion ,International Journal of Nanomedicine ,Drug Discovery ,Copolymer ,Polyamines ,Animals ,Humans ,Polyethyleneimine ,Particle Size ,Original Research ,Polyethylenimine ,cell transfection ,Cell Death ,Organic Chemistry ,Layer by layer ,General Medicine ,DNA ,021001 nanoscience & nanotechnology ,Biodegradable polymer ,Combinatorial chemistry ,Polyelectrolytes ,Polyelectrolyte ,0104 chemical sciences ,Solutions ,HEK293 Cells ,chemistry ,Polymerization ,biodegradable polymers ,Hydrodynamics ,NIH 3T3 Cells ,0210 nano-technology - Abstract
Lingxiao Xie, Xiong Ding, Rachel Budry, Guangzhao Mao Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA Background: The layer-by-layer (LbL) assembly method offers a molecular level control of the amount and spatial distribution of bioactive molecules. However, successful clinical translation of LbL film technology will most certainly require a better understanding and control of not only the film assembly process, but also film disassembly kinetics in physiologic conditions. Purpose: This work focuses on the understanding and control of degradation properties of LbL films for localized gene delivery. Methods: Bioreducible poly(amido amine)s (PAAs) containing cystaminebisacrylamide (CBA), methylenebisacrylamide, and 5-amino-1-pentanol (APOL) were synthesized by Michael addition polymerization for the construction of bioreducible LbL films capable of sequential gene delivery. Results: The synthesized PAAs were screened for desirable buffering capacity, cell transfection, and cytotoxicity characteristics together with 25 kDa branched polyethylenimine (PEI) and cross-linked 800 Da PEI. By screening the various polycations we were able to identify a copolymer of CBA and APOL for the subsequent construction of the LbL films. By incorporating a highly transfecting polycation and a nondiffusing polycation we were able to improve the overall transfection of HEK293 and MC3T3 cells from the bioreducible LbL films. We also demonstrated the dual-stage release and transfection of two different DNAs from the LbL films. Conclusion: The results indicate that LbL films consisting of bioreducible PAAs and non-diffusing polyelectrolytes have excellent degradation properties for the development of LbL coating technology for localized gene delivery applications. Keywords: biodegradable polymers, cell transfection, interlayer diffusion, localized gene delivery, polyelectrolyte multilayers, sequential release
- Published
- 2018