Small upconversion-ruthenium nanohybrids for cancer theranostics

Photoresponsive drug delivery systems have great potential for improved cancer therapy. However, most of the currently available drug-delivery nanosystems are relatively large and require light excitation with low tissue penetration. Here, we designed a near infrared responsive drug delivery system by loading [Ru(terpyridine)(dipyridophenazine)(H2O)]2+ (Ru(tpy)DPPZ) in azobenzene-modified mesoporous silica coated NaGdF4:Nd0.01/Yb0.2/Tm0.01 upconversion nanoparticles (azo-mSiO2-UCNPs). Upon 808 nm excitation, the generated ultraviolet and blue upconversion luminescence induced a reversible cis-trans isomerization of azobenzene for on-demand release of Ru(tpy)DPPZ. Imaging of both the UCNPs and Ru(tpy)DPPZ revealed targeted drug delivery to the nucleus of MCF-7 breast cancer cells, inducing DNA damage and concomitant cell destruction. Considering that cell nuclei are the core of cellular transcription and the main site of action for multiple chemotherapeutic drugs, our NIR-excitable and small (10 nm diameter) nanohybrids can potentially become highly versatile tools for targeted cancer theranostics.