Cationic dendron-bearing lipid/CD151 siRNA complex inhibits osteosarcoma metastasis by down-regulating matrix metalloproteinase-9

Abstract

Small interfering ribonucleic acids (siRNAs) hold immense potential for use in cancer treatment. Cationic dendron-bearing lipids (CDLs) are effective siRNA delivery systems. We previously demonstrated a CDL composed of cis-9-octadecenoic acid and a first-generation polyamidoamine dendron as a potential siRNA nanocarrier with high transfection efficiency and low in vitro cytotoxicity. CD151, one of tetraspanins, facilitates cancer metastasis via an as yet unknown mechanism. In the present study, CDL was employed as an effective delivery system of siRNA_CD151 for inhibition of osteosarcoma metastasis in vivo. CDL/siRNA_CD151 exhibited excellent cytocompatibility with 143B cells and showed a good hemocompatibility in vitro. Further, it inhibited migration and invasion of 143B cells, and OS metastasis in vivo, which was mediated via down-regulation of CD151 and matrix metalloproteinase-9 (MMP-9) expressions. In addition, it showed an excellent safety profile in vivo. The results of the present study suggest CDL as a promising siRNA delivery nanovehicle targeting CD151 with a favorable safety profile and fascinating effectiveness for treatment of OS metastasis.