Large amino acid transporter 1 mediated glutamate modified mesoporous silica nanoparticles for chemophotothermal therapy

Abstract

Glutamic acid modified Pluronic P123 (P123-G) was synthesized to coat hydrophobic mesoporous silica nanoparticles (PGMSN) aiming to target large amino acid transporter 1 (LAT1) overexpressed cancer cells. We discovered that, once internalized, PGMSN could be transported out of the cells with their cargo, and the exported nanoparticles were then taken up by neighboring cells. This intercellular delivery of particles led to a deeper tumor penetration, presumably through tandem cycles of LAT1 mediated endocytosis and exocytosis. Taking advantage of high drug loading capability of MSN, a kind of cyanine dye Cypate acting as a photothermal converting agent was loaded into MSN along with the chemotherapeutic drug doxorubicin hydrochloride (DOX) to improve the anti-cancer effect by the combination of chemotherapy and photothermal therapy (PTT). Both DOX and Cypate stably dispersed in the pores of MSN, and the coating of P123-G serving as diffusion barrier blocked drug preleakage. The system possessed pH and near-infrared (NIR) light dual-responsive DOX release property. Additionally, PGMSN exhibited targeted PTT effect which strengthened cytotoxic activity of the system due to the enhanced endocytosis. So the deep tumor penetration and targeted PTT effect made PGMSN especially suitable for cancers overexpressing LAT1 receptors.