Gene Expression, Biodistribution, and Pharmacoscintigraphic Evaluation of Chondroitin Sulfate−PEI Nanoconstructs Mediated Tumor Gene Therapy

Citations Over TimeTop 10% of 2009 papers

Abstract

Tumor-specific gene delivery constitutes a primary challenge in nonviral mediated gene therapy. In this investigation, branched polyethylenimine (bPEI, 25 kDa) was modified by forming nanoconstructs with a natural polysaccharide, chondroitin sulfate (CS), to impart site-specific property. A library of CS-PEI (CP) nanoconstructs was fabricated by altering the content of CS and evaluated in terms of size, surface charge, morphology, pDNA loading efficiency, pDNA release assay, pDNA protection study, cytotoxicity, and transfection efficiency. In vitro transfection efficiency of CP nanoconstructs was examined in HEK293, HEK293T, HepG2, and HeLa cell lines, while their cytotoxicity was investigated in HepG2 and HeLa cells. DNase I protection assay showed that the plasmid was protected from degradation over a period of time. The CP nanoconstructs possess significantly lower toxicity and enhanced transfection efficiency compared to PEI (25 kDa) and commercial transfection reagents (i.e., superfect, fugene, and GenePORTER 2). Further, the CP nanoconstructs were also found to transfect cells in serum-containing medium. In vivo studies were carried out with pDNA loaded CP-3 nanoconstruct after intravenous (iv) injection in Ehrlich ascites tumor (EAT)-bearing mice. The outcome revealed higher concentration of CP-3 nanoconstruct in tumor mass. These findings demonstrate that CP nanoconstructs could be exploited as carriers for nanomedicine for efficient management of solid tumor.

Related Papers

• → The biodistribution of NC100668 and the effect of excess NC100668 on the biodistribution and kidney retention of 99mTc-NC100668 in the rat(2007)4 cited
• Synthesis and biodistribution studies of [~(99)Tc~m(CO)_3-EC] complexes(2004)
• Preparation and Biodistribution of ~(99)Tc~m-HEDTMP(2002)
• → Synthesis, hypoxic radiosensitization and biodistribution of N- (5-nitroindazole-3-formyl) tyrosine sodium(2015)
• An in vivo study of the biodistribution of gold nanoparticles after intervaginal space injection in the tarsal tunnel(2016)