Multifunctional Gd-based mesoporous silica nanotheranostic for anticancer drug delivery†
Abstract
A nanosized drug delivery system based on mesoporous silica nanoparticles functionalized with highly stable GdDOTAGA complexes, rhodamine dyes and PEG3000 molecules was synthesized. The external side of the PEG was also functionalized with azadibenzocyclooctyne moieties in order to exploit the bioorthogonal Cu(I)-free click chemistry targeting approach after metabolic labeling of cell-surface glycans with azido-mannose molecules. The particles’ pores were then impregnated with the chemotherapeutic drug mitoxantrone to add a therapeutic function to the nanosystem. The bioorthogonal targeting of the nanotheranostic probe on mannose-treated breast cancer MCF7 and TS/A cells showed a minimal difference between cells metabolically labeled or not. However, MRI experiments on labeled MCF7 cells showed a significant 200% contrast enhancement with respect to untreated cells, thus confirming the high contrast efficiency even when the cells were incubated with nanoparticles for a few minutes. Moreover, administration of the nanoprobe to MCF7 cultures resulted in a higher cytotoxicity in comparison to the free drug at a similar concentration, confirming the successful delivery of the drug.