Development of poly(ethyleneimine) grafted amphiphilic copolymers : Evaluation of their cytotoxicity and ability to complex DNA

Titelangaben

Diaz, Ivonne L. ; Jérôme, Valérie ; Freitag, Ruth ; Perez, León D.:
Development of poly(ethyleneimine) grafted amphiphilic copolymers : Evaluation of their cytotoxicity and ability to complex DNA.
In: Journal of Bioactive and Compatible Polymers. Bd. 36 (2021) Heft 6 . - S. 447-463.
ISSN 1530-8030
DOI: https://doi.org/10.1177/08839115211053925

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Abstract

Poly(ethyleneimine) (PEI) is one of the most widely used cationic polymers for gene delivery. The high molecular weight polymer, which is commercially available, is highly efficient but also very cytotoxic. The reduction in charge density by using nonlinear architectures based on low molecular weight (LMW) PEI is a promising approach to produce safer DNA-vectors. Herein, a group of cationic graft copolymers with different composition containing a hydrophobic biocompatible backbone and LMW linear PEI (lPEI) grafts obtained by ring opening polymerization and click chemistry was studied. The self-assembly and DNA complexation behavior of these materials was analyzed by the gel retardation assay, zeta potential measurements, and dynamic light scattering. The copolymers formed positively charged particles in water with average sizes between 270 and 377 nm. After they were added to DNA in serum-free medium, these particles acquired negative/near-neutral charges and increased in size depending on the N/P ratio. All copolymers showed reduced cytotoxicity compared to the 25 kDa lPEI used as reference, but the transfection efficiency was reduced. This result suggested that the cationic segments were too small to fully condense the DNA and promote cellular uptake, even with the use of several grafts and the introduction of hydrophobic domains. The trends found in this research showed that a higher degree of hydrophobicity and a higher grafting density can enhance the interaction between the copolymers and DNA. These trends could direct further structural modifications in the search for effective and safe vectors based on this polycation.