Cell uptake and anti-tumor effect of liposomes containing encapsulated paclitaxel-bound albumin against breast cancer cells in 2D and 3D cultured models

摘要

Paclitaxel (PTX), a water insoluble anticancer drug, was incorporated into the inner aqueous core of a liposome without the aid of an organic co-solvent,vianon-covalent binding with bovine serum albumin (BSA) to form a PTX-BSA liposome. In the present study, PTX-BSA-liposomes are shown to have potent effects on human-derived breast cancer cell lines, MCF-7?cells and MDA-MB-231?cells, in 2D monolayer cultured cells and 3D multicellular tumor spheroids. The results of cellular uptake studies in 2D monolayer cultured cells clearly showed that the fluorescence derived from dansyl-l-asparagine (DNSA), a model encapsulated drug, and Cy5-cholesterol (a model membrane) of DNSA-BSA-liposome were observed inside the cells. Along with cell uptake, the PTX-BSA-liposomes exhibited a concentration-dependent cytotoxicity against MCF-7 and MDA-MB-231?cells but the IC50 value of the PTX-BSA-liposomes was higher than that of free PTX and nab-PTX (albumin-bound PTX nanoparticle). On the other hand, PTX-BSA-liposome, as in the cases of free PTX and nab-PTX, inhibited cell growth in both 3D MCF-7 and MDA-MB-231 tumor spheroids, indicating that PTX-BSA-liposomes penetrated into the tumor spheroid. These results suggest that PTX-BSA-liposomes are an organic solvent free PTX formulation that would have potent anti-proliferative effects against breast cancer.