Bioreducible Cationic Poly(amido amine)s for Enhanced Gene Delivery and Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Abstract

The development of efficient and safe gene delivery carriers has been a major challenge in the clinical application of non-viral gene therapy. Herein, we report novel bioreducible poly(amido amine)s for the efficient delivery of genetic material such as plasmid DNA. A library of 34 different bioreducible polymer compounds was synthesized and screened to find lead materials for in vitro gene transfection. Our lead material (CBA-106) allows effortless polyplex formation with genetic materials by electrostatic interactions at the weight ratio of 1:5 (DNA/polymer). Polyplexes were further characterized by DLS and AFM analysis. Enhanced serum stability and bioreducibility under physiological conditions were confirmed, in addition to low cellular cytotoxicity. When compared with a commercially available gene delivery carrier (Lipofectamine 2000), CBA-1 06 shows comparable or even surpassing gene transfection efficiency. Furthermore, BMP-2 plasmids were efficiently delivered to tonsil-derived mesenchymal stem cells (TMSCs) for osteogenic commitment in vitro and in vivo. Taken together, our results clearly demonstrate the potential of novel bioreducible polymeric systems for gene delivery applications. We suggest that our system can provide a valuable platform for the broad application of gene regulation in cell therapy and regenerative medicine.

Mildly Cross-Linked Dendrimer Hydrogel Prepared via Aza-Michael Addition Reaction for Topical Brimonidine Delivery

“…35 Each set of samples was subjected to compression and shear stress at 25 °C. An amplitude sweep test was performed to ensure that all the measurements were conducted within the linear viscoelastic region.…”

“…28–32 Also, the cationic dendrimers, for example, polyamidoamine dendrimer (PAMAM), can be preferentially captured at the negatively charged corneal surface and therefore enhance the permeability of the formulations. 33–35 In-situ forming hydrogels are also often used as topical drug delivery systems because of ease of administration. 36, 37 The application of hydrogels can result in prolonged pre-corneal residence time and increased ocular bioavailability.…”

Novel polyethyleneimine-R8-heparin nanogel for high-efficiency gene delivery in vitro and in vivo

“…Recently, nonviral vectors have attracted more attention in gene therapy. Nonviral vectors, such as cationic polymers, dendrimers, lipids and peptides, are characterized by low immunogenicity and facile fabrication and thus used as promising gene delivery system (Elsabahy et al., 2011 ; Yin et al., 2014 ; Jeong et al., 2016 ).…”

Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor

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