The in vivo distribution of
antitumor drugs is usually lack of selectivity, and thus, leading to a low efficacy of
chemotherapy on
cancers and high toxicity to normal cells. Receptor-mediated targeting
liposome with pH-sensitivity as a dual drug delivery system is one of the efficient approaches to overcome the disadvantages. The study was to synthesize a novel smart polymeric material (folate-poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine, F-PEOz-DSPE), which can combine with the
folate-receptor (FR) over-expressed on
cancer cells and respond to pH changes in endosome-lysosome system in
cancer cells to rapidly release drug simultaneously. The
F-PEOz-DSPE was synthesized by the method of asymmetric synthesis of organic
polymer and characterized by IR, (1)H-NMR, electrospray ionization (ESI)-MS and gel permeation chromatography (GPC). To investigate the properties of targeting and pH-sensitivity of
F-PEOz-DSPE, blank
liposomes, blank fluorescently labeled
liposomes and
doxorubicin (DOX)-loaded
liposomes containing
F-PEOz-DSPE or PEOz-
DSPE or
DSPE were prepared. The cytotoxicity, cellular uptake and
drug cumulative release in vitro were investigated. Blank
liposomes modified with PEOz block had little cytotoxicity in vitro. The
liposomes containing
F-PEOz-DSPE showed a higher affinity to human
ovarian cancer cell SKOV3, a FR(+)
cancer cells, than those with PEOz-
DSPE. A higher
drug cumulative release from DOX-loaded
liposomes containing
F-PEOz-DSPE or PEOz-
DSPE in vitro was found in
phosphate buffered saline at pH 5.0 medium than at pH 7.4. These results indicate that
F-PEOz-DSPE exhibits selective targeting, pH-sensitivity and little cytotoxicity, and may be a promising polymeric material for dual receptor and pH-sensitive targeting
liposome.