title: Structure-biocompatibility and transfection activity relationships of cationic polyaspartamides with (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups.
abstract: A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide. The resulting polyaspartamides have moderate amphiphilic properties. Relationships between the structure and ratio of side groups and in vitro properties of polyaspartamides, including their cytotoxic and membrane-damaging activity towards human cell lines, primary skin fibroblasts and erythrocytes, were established and discussed. Cationic polyaspartamides vary in their DNA-binding, condensing and nuclease-protecting characteristics depending on the concentration ratio of (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups. Effective cell transfection was achieved upon polyaspartamide-mediated plasmid DNA delivery in serum-free medium in the presence of chloroquine. Effect of serum proteins adsorption onto polyaspartamide based polyplexes, and the role of concentration of polyplexes in culture medium in their colloidal stability and transfection process were demonstrated. Synthesized polyaspartamides are biocompatible and long-acting gene carriers, which are applied to cells after dilution and without washing, thus providing transfection level comparable to that of commercial transfection reagent.
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Diana
authors.initials: D
authors.lastname: Salakhieva
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Vesta
authors.initials: V
authors.lastname: Shevchenko
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Németh
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary.
authors.forename: Benjámin
authors.initials: B
authors.lastname: Gyarmati
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary. Electronic address: aszilagyi@mail.bme.hu.
authors.forename: András
authors.initials: A
authors.lastname: Szilágyi
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: tabdulli@gmail.com.
authors.forename: Timur
authors.initials: T
authors.lastname: Abdullin
mesh_terms: D000327:Adsorption; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry; D004337:Drug Carriers; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D061251:Primary Cell Culture; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
chemical_list: D000577:Amides; D001798:Blood Proteins; D004337:Drug Carriers; D010455:Peptides; C025252:poly-DL-succinimide; D001224:Aspartic Acid; D004247:DNA
keywords: Cationic polyaspartamides; Dilution effect; Plasmid DNA delivery; Poly(aspartic acid); Serum proteins; Structure–activity relationship