Functional study of dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) gene delivery vector for tumor therapy

Abstract

The obstacle of gene therapy is the shortage of efficient delivery system. The development of the gene delivery system with high transfection efficiency and low toxicity appears to be crucial. Recently, we reported that the dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) (DPD) can be potentially used as efficient gene vector. Herein, DPD was systematically studied for its potential in tumor gene therapy. DPD was synthesized and characterized by agarose gel electrophoresis, particle size and zeta potential. The particle size and zeta potential of the DPD/enhanced green fluorescent protein (pEGFP-C1) plasmid complexes at various N/P ratios were 130-150 nm and about 40 mV, respectively. The results showed that DPD exhibit a higher transfection effect compared with Lipofectamine 2K (Lipo 2K), a commercialized vector. The possibility of DPD in gene therapy was evaluated using p53, a gene that has been wildly applied in the research of cancer gene therapy. DPD/pEGFP-C1-p53 complex was found to be able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis. Moreover, the tumor growth was found to be restrained when DPD/pEGFP-C1-p53 complex was used in a xenograft MCF7 tumor model in vivo. These observations indicated that DPD/pEGFP-C1-p53 complex may be considered to be an efficient delivery system for tumor gene therapy.

Current Progress in Gene Delivery Technology Based on Chemical Methods and Nano-carriers

“…Cationic polymer-based gene carriers (polyplexes) showed good biodegradability, low toxicity, triggered nucleic acid release, structural diversity and relatively higher transfection efficiency than liposomes 85-87, and the gene delivery process of polymers is described in Figure 3 . Many kinds of polymers have therefore been investigated for gene delivery, such as chitosan, PEI, polylysine, polyamino ester and so on 88-92.…”

Protonation behavior of dextran amino acid esters

“…Apart from naturally occurring polycations like chitosan that may be applied in various fields (e.g., in wastewater treatment [1] and as coantibiotics [2]), interest lies in chemically modified polysaccharides, like cationic cellulose [3], starch [4], and dextran derivatives. Polycationic dextran derivatives have gained great interest in the field of gene delivery [5,6] due to the low toxicity and high biodegradability of dextran [7]. For gene delivery, polymers have to bear protonable amino groups due to the necessity of polycationic moieties that play an important role in various steps of gene delivery [8].…”

Water soluble cationic dextran derivatives containing poly(amidoamine) dendrons for efficient gene delivery

“…Up to now, some cationic dextran derivatives have been synthesized and investigated for gene delivery. For example, Li et al (2013) prepared dextrangraft-poly((2-dimethyl amino)ethyl methacrylate) as an efficient delivery system for tumor gene therapy; Thomas, Rekha, and Sharma (2010) prepared cationic dextran-protamine conjugate as a haemocompatible and nonviral gene vector; Yeo et al (2014) conjugated spermine onto dextran for delivering gene to the lung of mouse via intranasal route. However, the efficiency of gene delivery by these cationic dextran derivatives is still relatively low when compared to commonly used polyethylenimine (PEI) or cationic lipids.…”