Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model

Abstract

Gene therapy provides a promising approach for cancer treatment. Earlier studies suggested that poly-L-lysine-modified iron oxide nanoparticles (IONP-PLL) might be a promising gene delivery system that can transfect DNA efficiently in vitro and in vivo. In this study we used IONP-PLL as gene carriers to deliver the NM23-H1 gene, the first suppressor gene of cancer metastasis, to tumor cells in vivo. The intravenous injection of IONP-PLL carrying NM23-H1-GFP plasmid DNA significantly extended the survival time of an experimental pulmonary metastasis mouse model. In the IONP-PLL/NM23-H1-GFP-treated group, metastasis was clearly suppressed compared with the group treated with free NM23-H1-GFP plasmid. Furthermore, this gene therapy combined with cyclophosphamide treatment resulted in longer survival times and greater suppression of metastasis growth. In conclusion, treatment with IONP-PLL nanoparticles incorporating the NM23-H1gene is an efficient gene therapy method, and it is even more effective in combination with chemotherapy. This approach appears to be a promising strategy for treatment of metastatic tumors.

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

“…Deliver of IONP-PLL-a novel non viral vector for efficient gene delivery along with plasmid Nm23 in to target tissue reduces lung metastasis of B16F10 melanoma cell line injected animal (Li et al, 2009). This proves that using nano-vectors targeting tissues can be useful systemic gene therapy.…”

“…This proves that using nano-vectors targeting tissues can be useful systemic gene therapy. Combination of therapy such as gene therapy, chemotherapy and cyclophosphamide has been reported to increase survival time and also with greater suppression of metastasis cascade (Li et al, 2009). Multifunctional role of metastasis suppressor gene Nm23 family provides advancement in the field of new approach on targeted therapy.…”

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

“…An inhibition of the Nme enzymatic activity by small molecule inhibitors was initially intended, but the available polyphenols such as ellagic acid (Buxton 2008), although widely discussed to be beneficial in cancer therapy, are unspecific kinase inhibitors and show low potency. Gene therapy approaches were successful preclinically (Li et al 2006;Li et al 2009) but remain clinically intractable. A variety of alternative approaches have been pursued.…”

Investigation on cellular interactions of astrocytes with zinc oxide nanoparticles using rat C6 cell lines

“…Research is undergoing world wide for the exploitation of ZnO NPs as a tool for biomedical application and therapeutic intervention owing to their high stability, inherent photoluminescence and wide bandgap semiconductor properties. Many studies project ZnO NPs as potential agents for various biomedical applications like bio-sensing [4], cancer therapy, [5,6] gene targeting [7,8] and drug delivery [9,10]. Also, there are studies stating the use of ZnO NPs in cell imaging [11], in diabetes treatment as dietary modulators, as cholesterol biosensors [12] and as anti-inflammatory agents [13].…”