Hierarchically designed hybrid nanoparticles for combinational photochemotherapy against a pancreatic cancer cell line

Abstract

Here, we report the formulation of hybrid nanoparticles consisting of aggregated gold nanoparticles (GNPs) impregnated into a gemcitabine-polymer conjugate matrix that exhibit synergistic photo-chemo-therapeutic activity against pancreatic cancer. Well-defined, sub-100 nm hybrid NPs were successfully formulated and their photothermal conversion efficiency was evaluated, which was found to be as high as 63% in the red-visible spectrum. By varying the GNP and GEM-polymer feed, it was possible to control the red-shifting of the surface plasmon resonance at therapeutically relevant wavelengths. The hybrid NPs exhibited significant cytotoxicity against MiaPaCa-2 cells with a half-maximal inhibitory concentration (IC50) of 0.0012 mg mL-1; however the IC50 decreased by a factor of 2 after the cells were irradiated with a continuous wave red laser for 1 min (1.4 W cm-2). Although the irradiation of the aggregated GNPs loaded in the hybrid NPs produced a higher thermal effect for the same amount of non-loaded GNPs, the IC50 of the hybrid NPs was significantly lower than that of the free GNPs, hence indicating a synergistic effect of the polymer bound GEM and the GNPs.