Maleimide-Functionalized Liposomes for Tumor Targeting via In Situ Binding of Endogenous Albumin.

Albumin, the most abundant protein in plasma, has been widely used in drug delivery studies. Here, we developed maleimide-functionalized liposomes (Mal-Lip) that can bind to endogenous albumin to improve the tumor targeting efficiency of liposomes. Transmission electron microscopy and gel electrophoresis studies showed that albumin can bind to Mal-Lip due to the chemical coupling of the albumin thiol groups with the maleimide group. Both conventional liposomes and Mal-Lip showed minimal cytotoxicity within the tested range of lipid concentrations, indicating that the maleimide functionality did not increase the toxicity of liposomes to various cells. Mal-Lip was taken up by 4T1 cells to a greater extent than conventional liposomes, and Mal-Lip accumulated in 4T1 tumors in mice more than conventional liposomes after intravenous injection. These results suggest that the maleimide group can improve the tumor targeting efficiency of liposomes in vivo by binding to endogenous albumin in situ. However, the maleimide group also enhanced the uptake of Mal-Lip by Raw264.7 cells and shortened their time in circulation, indicating that further studies should be performed to prevent elimination of Mal-Lip by the immune system.