p53 gene therapy of human osteosarcoma using a transferrin-modified cationic liposome

Abstract

Gene delivery via transferrin receptors, which are highly expressed by cancer cells, can be used to enhance the effectiveness of gene therapy for cancer. In this study, we examined the efficacy of p53 gene therapy in human osteosarcoma (HOSM-1) cells derived from the oral cavity using a cationic liposome supplemented with transferrin. HOSM-1 cells were exposed to transferrin-liposome-p53 in vitro, and the growth inhibition rate, expression of p53 and bax, and induction of apoptosis were measured 48 hours later. Treatment of HOSM-1 cells with transferrinliposome-p53 resulted in 60.7% growth inhibition. Wildtype p53 expression and an increase in bax expression were observed following transfection with transferrinliposome-p53, and 20.5% of the treated HOSM-1 cells were apoptotic. In vivo, the HOSM-1 tumor transplanted into nude mice grew to 5 to 6 mm in diameter. Following growth of the tumor to this size, transferrin-liposome-p53 was locally applied to the peripheral tumor (day 0) and then applied once every 5 days for a total of six times. During the administration period, tumor growth did not occur, and the mean tumor volume on the last day of administration (day 25) was 10.0% of that in the saline control group. These results suggest that p53 gene therapy via cationic liposome modification with transferrin is an effective strategy for treatment of osteosarcoma. [Mol Cancer Ther 2005;4(4):625 -31]

Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

“…For cell-specific gene delivery, cell type-specific surface molecules and their antibodies would be useful, and a number of cell-specific gene delivery vectors have been developed (Germershaus, et al, 2006;Chiu, et al, 2004;Liu, et al, 2007). For cancer gene therapy, tumor suppressor genes such as p53 gene and suicide genes such as herpes simplex virus thymidine kinase gene were well studied; and those genes reported to suppress tumor growth by tumor specific gene delivery vector such as transferrin-modified cationic liposome (Nakase, et al, 2005;Neves, 2006).…”

Chondroblastic osteosarcoma secondary to fibrosarcoma: A case report and literature review

“…The study by Nakase et al suggested that p-53 gene therapy via cationic liposome modification with transferrin is an effective strategy for the treatment of osteosarcoma. However, further research is required to improve the clinical efficacy (21). Immunotherapy has great potential for treating osteosarcomas, promising improved patient survival rates and quality of life (22).…”

Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo

“…Active targeting of tumor tissue by liposomes can be achieved by modifying the liposome with addition of a targeting ligand, such as an antibody and a peptide. [48][49][50][51] However, the problem with these systems is that the majority of the liposomes are still cleared by the reticuloendothelial system, resulting in short half-lives, low accumulation in tumor tissue, and unwanted deposition in the liver and spleen. To achieve a specific therapeutic effect, both a prolonged blood circulation time and an active tumortargeting effect are essential for an ideal drug delivery system.…”