Multifunctional Gd-based mesoporous silica nanotheranostic for anticancer drug delivery

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.