Biopolymer-directed synthesis of high-surface-area magnetite colloidal nanocrystal clusters for dual drug delivery in prostate cancer

Abstract

Typical biopolymers, including soybean, casein, γ-poly(glutamic acid) (PGA), agarose and chitosan, were investigated as stabilizers in the synthesis of nanoporous magnetite colloidal nanocrystal clusters (MCNCs) by the hydrolysis and reduction of iron(III) chloride hydrate in ethylene glycol at 200 °C. The cluster sizes, morphologies, porous structures and magnetization of the resulting MCNCs were significantly affected by the different biopolymers. Of those members, soybean protein enabled the formation of spongy MCNCs with a surprisingly high specific surface area of 207 m² g⁻¹ and a characteristic mesopore diameter of 6.3 nm. Use of the other biopolymers (e.g. PGA and casein) led to the formation of MCNCs with lower specific surface areas (>100 m² g⁻¹) but considerably enhanced saturation magnetizations (∼60 emu g⁻¹). Our results further shed light on the role played by the biopolymers in the structural evolution of the porous nanocrystal clusters. Analysis by characterizations of TEM and TGA showed that the decomposition of the biopolymer chains may have occurred during the transition from solid to porous clusters. As such, it is most likely that the biopolymers including soybean, casein and PGA serve as sacrificial templates to direct the formation of high-surface-area MCNCs. Taking into account the comprehensive properties of the different MCNCs, the PGA-stabilized MCNCs were selected as a drug delivery vehicle to simultaneously encapsulate therapeutic docetaxel (DOC) and ceramide (CER) via the hydrogen bonding interaction, for the treatment of prostate cancer. The inhibitory and apoptotic effects of the loaded DOC and CER co-delivered within MCNCs were evaluated in the prostate cancer cell line (PC-3) in vitro.