Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model.
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.
Li
Z
Z
Cancer Research Institute, Central South University, Changsha, Hunan, The People's Republic of China.
Xiang
J
J
Zhang
W
W
Fan
S
S
Wu
M
M
Li
X
X
Li
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000633:toxicity; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D054778:NM23 Nucleoside Diphosphate Kinases / Q000008:administration & dosage* / Q000378:metabolism; D053758:Nanoparticles / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D000077022:Survivin; D029961:Zebrafish Proteins
D000970:Antineoplastic Agents; C541681:Birc5a protein, zebrafish; D051034:Inhibitor of Apoptosis Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D000077022:Survivin; D029961:Zebrafish Proteins; C517938:NME1 protein, human