ABSTRACT
Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)-DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl3. DOX-R-MSNs could effectively maintain their structural integrity in a physiological environment for 7 days and show an enhanced in vitro T1-MR imaging signal for the Gd-DOTA complex. Upon 660 nm laser irradiation, the release rate of DOX from DOX-R-MSNs remarkably increased along with the disintegration of the gatekeeper, whereas DOX release was significantly retarded without irradiation. When DOX-R-MSNs were intravenously injected into tumor-bearing mice, they were effectively accumulated in tumor tissue, which was demonstrated using MR imaging. In addition, tumor growth was significantly suppressed by DOX-R-MSNs, allowing for site-specific release of DOX in a photodynamically maneuvered manner. Overall, these results suggest that R-MSNs have potential as drug carriers for MR imaging-guided photodynamic chemotherapy.
Subject(s)
Magnetic Resonance Imaging , Nanoparticles/chemistry , Neoplasms, Experimental/drug therapy , Photochemotherapy , Reactive Oxygen Species/chemistry , Silicon Dioxide , Animals , Cell Line, Tumor , Doxorubicin/administration & dosage , Drug Delivery Systems , Male , Mice , Mice, NudeABSTRACT
A pH-responsive, multiple chemotherapeutic agent derived nanocarrier has been synthesized by conjugating doxorubicin, indomethacin, and folate to the backbone of norbornene polymer. Drug molecules are connected to the norbornene backbone by an ester linker to demonstrate the pH-responsive capabilities. The complete chemical and biological properties of the new norbornene-based polymeric nanocarrier, intended for combination cancer chemotherapy, are discussed.
