In this study we present the synthesis of a new theranostic system consisting of a core-shell structured nanoceramic-drug conjugate that can potentially combine chemotherapeutic, targeting, diagnostic and radio dose enhancing features in cancer treatment. The conjugate is made of α-Bi2O3 nanoparticles (NPs) which were first coated with (3-aminopropyl)trimethoxysilane (APTMS) to form a core-shell structure and then attached with methotrexate (MTX) through amidation between the amine moieties on the shell and the carboxylic acid groups on MTX. While α-Bi2O3 NPs with high effective atomic number can serve as both contrast agent and radiosensitiser in dose enhancement radiation therapy, MTX as an anti-cancer drug provides chemotherapeutic features and can selectively target cancer cells. The α-Bi2O3 NPs were firstly formed through a simple precipitation route, and were found through X-ray diffraction to be single phase. Fourier transform infrared spectroscopy and electron microscopy were then used to confirm the presence of a self-assembled layer of APTMS which aided in increasing their dispersibility compared to uncoated α-Bi2O3 NPs. Ultraviolet-visible spectroscopy was also used to show that 4% of the APTMS (mole ratio) has bound MTX leading to a conjugate with a size of 50 nm in diameter. The capability of α-Bi2O3 NPs to provide diagnostic features was proven with computed tomography (CT) scans and the degree of internalization of the uncoated, APTMS coated and MTX coated bismuth oxide NPs into 9L glioma cells was examined by flow cytometry analysis. Clonogenic assays exhibited a toxicity of 97% for the α-Bi2O3-APTMS-MTX conjugate, significantly higher than the initial components, which showed lower cancer cell death rates.
Available at: http://works.bepress.com/stephanie_corde/26/