Influence of Alkyl Chains of Modified Polysuccinimide-Based Polycationic Polymers on Polyplex Formation and Transfection

Autor(es)

Kravicz, Marcelo H. ^{[1, 2]} ; Balogh, Debora T. ^[3] ; Kar, Mrityunjoy ^[2] ; Wedepohl, Stefanie ^[2] ; Bentley, Maria Vitoria L. B. ^[1] ; Calderon, Marcelo ^{[4, 2, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin - Germany

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, CP 369, BR-13560970 Sao Carlos, SP - Brazil

^[4] Ikerbasque, Basque Fdn Sci, Bilbao 48013 - Spain

^[5] Univ Basque Country UPV & HU, POLYMAT & Appl Chem Dept, Fac Chem, Paseo Manuel Lardizabal 3, Donostia San Sebastian 20018 - Spain

• Tipo de documento: Artigo Científico
• Fonte: Macromolecular Bioscience; v. 19, n. 10 AUG 2019.
• Citações Web of Science: 0

Resumo

The development of polymers with low toxicity and efficient gene delivery remains a significant barrier of nonviral gene therapy. Modification and tuning of chemical structures of carriers is an attractive strategy for efficient nucleic acid delivery. Here, polyplexes consisting of plasmid DNA (pDNA) and dodecylated or non-dodecylated polysuccinimide (PSI)-based polycations are designed, and their transfection ability into HeLa cells is investigated by green fluorescent protein (GFP) expressing cells quantification. All cationic polymers show lower cytotoxicity than those of branched polyethyleneimine (bPEI). PSI and bPEI-based polyplexes have comparable physicochemical properties such as size and charge. Interestingly, a strong interaction between dodecylated polycations and pDNA caused by the hydrophobic moiety is observed in dodecylated PSI derivatives. Moreover, the decrease of GFP expression is associated with lower dissociation of pDNA from polyplexes according to the heparin displacement assay. Besides, a hydrophobization of PSI cationic derivatives with dodecyl side chains can modulate the integrity of polyplexes by hydrophobic interactions, increasing the binding between the polymer and the DNA. These results provide useful information for designing polyplexes with lower toxicity and greater stability and transfection performance. (AU)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático