MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

Abstract Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared ( S1-apMUC1 ) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced ( S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with 99m Tc ( S1-apMUC1-Tc ) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice.