A novel tumor-targeted thermosensitive liposomal cerasome used for thermally controlled drug release.

Drug carriers with tumor targeting and controlled release have strong prospects for application in safe and efficient chemotherapy. Among various carriers, liposomes have good biocompatibility and can enhance the uptake of drugs by cancer cells. However, traditional liposomes have no specific targeting to cancer cells and are prone to insufficient stability, causing early leakage of the drug. Accordingly, organic-inorganic hybrid phospholipid and thermosensitive phospholipid are deliberately introduced into a liposome system to enhance the morphological and structural stability of the liposomes while realizing thermally controlled drug release. Furthermore, modification with a targeting ligand (WSG-peptide) can endow liposomes with active targeting to ovarian carcinoma cells. First, WSG-peptide was grafted onto the hydrophilic terminal of phospholipid molecules, and the organic-inorganic hybrid cerasome-forming lipid (CFL) was synthesized via a two-step chemical reaction. Then, the WSG-grafted thermosensitive liposomal cerasome (c-LIP-WSG) was prepared by thin-film hydration method. The results showed that the c-LIP-WSG had excellent structural stability both in storage and in a simulated circulation environment. In vitro drug release confirmed that the liposomes exhibited thermally controlled release. Cell uptake experiments and living fluorescence imaging of SKOV-3 tumor-bearing nude mice confirmed that the WSG-peptide modified liposomes were provided with specific targeting properties for ovarian carcinoma.