Novel Chondroitin Sulfate-binding Cationic Liposomes Loaded with Cisplatin Efficiently Suppress the Local Growth and Liver Metastasis of Tumor Cells in Vivo

摘要: An increased level of chondroitin sulfate (CS) expression on the cell surface is often associated with malignant transformation and progression tumor cells. In this study, CSs expressed highly metastatic cells were used as a target for selective delivery anticancer drugs by polyethylene glycol (PEG)-coated liposomes that contained new cationic lipid 3,5-dipentadecycloxybenzamidine hydrochloride (TRX-20). We found PEG-coated TRX-20 (TRX-20 liposomes) bound preferentially to certain CSs, such CS B, D, E, whereas lacking showed no significant binding any glycosaminoglycans tested. vitro, liposomes, but not plain PEG avidly readily internalized LM8G5 ACHN cells, which express large amounts surface. When loaded cisplatin, they effectively killed CS-expressing in cisplatin-PEG totally ineffective. injected systemically, accumulated liver solid s.c. tumors. Therapeutic experiments mice bearing revealed cisplatin-loaded significantly more effective reducing local growth than or free cisplatin. Furthermore, markedly suppressed spreading liver, increasing survival time tumor-bearing mice. These results demonstrate CS-targeted novel represents potentially useful strategy prevent metastasis, particularly have enhanced CS.