Paclitaxel and di-fluorinated curcumin loaded in albumin nanoparticles for targeted synergistic combination therapy of ovarian and cervical cancers.

Abstract

Paclitaxel (PTX) encapsulated in albumin (Abraxane®) is an FDA approved frontline nano-formulation for treating advance metastatic pancreatic, lung and breast cancers. Currently in clinic, Abraxane® is being used as a one of the components of combination therapy regimens. On the other hand, difluorinated curcumin (CDF) is a novel and potent synthetic curcumin analogue that is being evaluated for several malignancies including pancreatic, liver, ovarian and breast cancers. To improve the bioavailability and targeting ability of hydrophobic PTX and CDF, we have encapsulated them in folic acid decorated bovine serum albumin nanoparticles, namely FA-BSA-PTX and FA-BSA-CDF, respectively. Both the formulations yielded uniform nano-sized particles with smooth surface morphology, negative surface potential and high drug loading efficiency. Due to heterogeneity and complexity of several cancers, combination regimens are becoming standard arsenals against several deadly cancers. To evaluate the synergistic anti-cancer effect of PTX and CDF, we assessed the combination therapy using intravenously administrable folate decorated albumin bio-conjugate nanoparticles against folate overexpressing ovarian and cervical cancers. Our results demonstrate that combination of FA-BSA-CDF with FA-BSA-PTX produced synergistic anticancer effect, augmented due to folate receptor mediated targeted uptake as well as induction of apoptosis. In conclusion, our preliminary studies show a promising nanomedicine platform for combination therapy for leading gynecological tumor, such as ovarian and cervical cancer.