Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers

Abstract

This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer. A consolidated double-layer formed by electrostatic interactions between the GO nanosheet and the PDA layer induced more controlled release kinetics which was well predicted by Higuchi model. In addition, Our MSNs exhibited stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent against cancer cells. In a cell test, multifunctional MSNs showed a low toxicity itself, but gave a high cytotoxicity against human epithelial neuroblastoma cells (SH-SY5Y) after loading cisplatin. Notably, GO-wrapped MSNs exhibited very effective drug delivery because GO wrapping enhanced their dispensability in aqueous solution, photothermal heating effect, and efficient endocytosis into cells. Furthermore, monoclonal antibody (anti-human epidermal growth factor receptor)-conjugated MSNs showed a higher specificity, which resulted in more enhanced anticancer effects in vitro. The current study demonstrated a reliable synthesis of multifunctional MSNs, endowed with fluorescent imaging, stimuli-responsive controlled release, higher specificity, and efficient cytotoxicity toward cancer cells.

Statement of significance: The current study demonstrated the reliable synthesis of multifunctional mesoporous silica nanoparticles (MSNs) with internal fluorescent conjugates and external polydopamine and graphene oxide (GO) layers. The combination of internal conjugates and external coating layers produced an effective pore closure effect, leading to controlled and sustained release of small drug molecules. Notably, GO wrapping improved the dispensability and cellular uptake of the MSNs, as well as enhanced drug-controlled release. Our multifunctional MSNs revealed very efficient drug delivery effects against human epithelial neuroblastoma cells by demonstrating several strengths: i) fluorescent imaging, ii) sustained and controlled release of small drug molecules, iii) efficient cellular uptake, cytotoxicity and specificity, and v) stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent.

Keywords: Controlled release; Efficient cytotoxicity; Fluorescent; Graphene oxide; Mesoporous; Photothermal heating; Polydopamine.