Bioreducible cationic random copolymer for gene delivery

Khan Muhammad, Jiaying Zhou, Ihsan Ullah, Jing Zhao, Ayaz Muhammad, Shihai Xia, Wencheng Zhang, Yakai Feng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cationic polymers have been widely investigated for gene delivery, although their low transfection efficiency and high cytotoxicity limit their application. We synthesized a bioreducible cationic random copolymer, poly(cystamine bisacylamide-aminoethyl piperazine)-co-poly(cystamine bisacylamide-histamine) (denoted as CBA-AEP-His) from N,N′-cystamine bis acrylamide (CBA) with aminoethyl piperazine (AEP) and histamine (His). CBA-AEP-His copolymer possesses disulfide linkages that endow it with redox-responsivity to the intracellular environment. This polymer efficiently condenses pZNF580 into complexes with the size of 160 ± 4 nm to 280 ± 5 nm and positive zeta potential of 20 ± 0.3 mV to 30 ± 0.4 mV. The gel-retardation assay shows that CBA-AEP-His can retard pZNF580 even at a low mass ratio of 1/1. The gene complexes were triggered to release pZNF580 when exposed to the reducing environment of dithiothreitol (DTT). CBA-AEP-His random copolymer presented higher buffer capacity owing to its His moieties, which protected pZNF580 from DNase degradation. The gene transfection results reveal that CBA-AEP-His can efficiently deliver pZNF580 and transfect EA. Hy926 cells. The MTT assay indicates that CBA-AEP-His and its complexes exhibit lower cytotoxicity than PEI25KDa. These results illustrate that CBA-AEP-His had promising properties for gene delivery, which may provide a suitable platform for the development of a non-viral gene carrier.

Original languageEnglish
Pages (from-to)2378-2389
Number of pages12
JournalPolymers for Advanced Technologies
Volume31
Issue number10
DOIs
StatePublished - 1 Oct 2020
Externally publishedYes

Keywords

  • bioreducible polymer
  • buffer capacity
  • endosomal escape
  • gene delivery
  • transfection efficiency

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