Multifunctional Redox-Responsive Mesoporous Silica Nanoparticles for Efficient Targeting Drug Delivery and Magnetic Resonance Imaging

The convenient modification of mesoporous silica nanoparticles (MSN) can provide great opportunities for constructing a new generation of nanocarriers with multiple functions. In the current study, we fabricated a new multifunctional drug delivery system based on MSN capped by gadolinium-based bovine serum albumin complex (BSA-Gd) and hyaluronic acid (HA) via reductive-cleavable disulfide bond. In this multifunctional nanoparticle (MSN-ss-GHA), BSA-Gd component was prepared by biomineralization and acted as both smart gatekeeper and contrast agent for magnetic resonance (MR) imaging, while HA served as the targeted molecule to improve the specific affinity of MSN-ss-GHA toward cancer cells. The successful fabrication of MSN-ss-GHA was demonstrated by a series of physicochemical characterization. The redox-sensitive drug release behavior of doxorubicin hydrochloride (DOX) loaded MSN-ss-GHA (DOX@MSN-ss-GHA) was also verified. Comparatively, the MSN-ss-GHA exhibited excellent biocompatibility and distinctly enhanced cell uptake by 4T1 cells. More importantly, the improved in vitro MR imaging ability of MSN-ss-GHA over that of Gd-DTPA was also confirmed. The results also suggested that the DOX@MSN-ss-GHA could efficiently deliver DOX into 4T1 cells and showed enhanced cytotoxicity as compared to that of nontargeted nanocarrier. The in vivo experiment also demonstrated the negligible toxicity of MSN-ss-GHA and improved antitumor suppression of DOX@MSN-ss-GHA. Thus, this multifunctional MSN-based theranostic agent holds potential for efficient redox-responsive targeting drug delivery and MR imaging.