chitosan-graft-branched polyethylenimine copolymers influence of degree of grafting on transfection behaviorchitosan-graft-branched表面共聚物接枝度对转染的影响行为.pdfVIP

Chitosan-Graft-Branched Polyethylenimine Copolymers: Influence of Degree of Grafting on Transfection Behavior 1 2 2 3 2 Daniele Pezzoli , Francesca Olimpieri , Chiara Malloggi , Sabrina Bertini , Alessandro Volonterio *, Gabriele Candiani1,2* ` 1 Unita Politecnico di Milano, Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali - INSTM, Milan, Italy, 2 Department of Chemistry, Materials and Chemical Engineering ‘‘Giulio Natta’’, Politecnico di Milano, Milan, Italy, 3 Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy Abstract Background: Successful non-viral gene delivery currently requires compromises to achieve useful transfection levels while minimizing toxicity. Despite high molecular weight (MW) branched polyethylenimine (bPEI) is considered the gold standard polymeric transfectant, it suffers from high cytotoxicity. Inversely, its low MW counterpart is less toxic and effective in transfection. Moreover, chitosan is a highly biocompatible and biodegradable polymer but characterized by very low transfection efficiency. In this scenario, a straightforward approach widely exploited to develop effective transfectants relies on the synthesis of chitosan-graft-low MW bPEIs (Chi-g-bPEIx) but, despite the vast amount of work that has been done in developing promising polymeric assemblies, the possible influence of the degree of grafting on the overall behavior of copolymers for gene delivery has been largely overlooked. Methodology/Principal Findings: With the aim of providing a comprehensive evaluation of the pivotal role of the degree of grafting in modulating the overall transfection effectiveness of copolymeric vectors, we have synthesized se