Paclitaxel-loaded pluronic F127/P123 silica nanocapsules with surface conjugated rhTRAIL for targeted cancer therapy

Abstract

A novel anticancer drug PFPSNT, paclitaxel (PTX)-loaded polymeric F127/P123 silica nanocapsules conjugated with TRAIL (tumor necrosis factor (TNF)-related apoptosis-inducing ligand), was designed and synthesized. Transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-vis absorption and particle size analysis revealed that the synthesized PFPSNT was a spherical particle with a size of 24 nm and excellent colloidal stability. Drug loading efficiency (DL%) and encapsulation ratio (ER%) were 0.39% and 26.5%, and its cumulative release profile was linear. In vitro study showed that PFPSNT had marked cytotoxic and apoptotic activities towards HepG2 (liver cancer cell line) and CaSki (cervical cell line) cells with the IC₅₀ values of 921.07 ng mL⁻¹ and 236.24 ng mL⁻¹, respectively. The antitumor efficacy of PFPSNT was evaluated by using a HepG2-xenografted BALB/c nu/nu mice model. In vivo study showed PFPSNT markedly inhibited HepG2 hepatocellular carcinoma, and its antitumor efficacy was more superior than those of TRAIL, PTX or PTX/F127/P123 silica nanocapsules. Our studies provided a novel strategy to synthesize anticancer nanodrugs with mutiple functions, and demonstrated that PFPSNT was a very effective anticancer drug. This novel nanodrug should be a promising drug for targeted cancer therapy to treat complex cancers.