Cell penetrating peptide conjugated polymeric micelles as a high performance versatile nonviral gene carrier

Buddhadev Layek, Jagdish Singh

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The major goal of this study is to design, synthesize, and evaluate linoleic acid and penetratin dual-functionalized chitosan (CS-Lin-Pen) as a nonviral gene carrier. The amphiphilic CS-Lin-Pen self-assembles to form cationic micelles in an aqueous environment. These polymeric micelles exhibited excellent hemocompatibility and cell viability, as evaluated by in vitro hemolysis and MTT assay, respectively. When CS-Lin-Pen micelles were added to plasmid DNA (pDNA) solution, the electrostatic interaction between the cationic micelles and anionic pDNA led to the formation of stable CS-Lin-Pen/pDNA polyplexes with ∼100 nm in size. The resultant polyplexes demonstrated ∼5-fold higher cellular uptake as compared to unmodified chitosan. Furthermore, CS-Lin-Pen micelles showed efficient protection of pDNA from DNase I attack and exhibited ∼34-40-fold higher transfection in comparison with unmodified chitosan in HEK 293, CHO, and HeLa cells. These findings illustrate that the CS-Lin-Pen micelles could be exploited as a potential nonviral vector for efficient gene therapy.

Original languageEnglish (US)
Pages (from-to)4071-4081
Number of pages11
JournalBiomacromolecules
Volume14
Issue number11
DOIs
StatePublished - Nov 11 2013

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