Real-time imaging of intracellular drug release from mesoporous silica nanoparticles based on fluorescence resonance energy transfer

In this study, a targeted cancer therapy imaging and sensing system is designed based on doxorubicin (DOX)-loaded green fluorescent mesoporous silica nanoparticles (FMSN) conjugated with folic acid (FA), by linking with alpha-amine-omega-propionic acid hexaethylene glycol (NH2-PEG-COOH). An in situ formation method is adopted to prepare luminescent MSNs, which then act as the donor for the fluorescence resonance energy transfer (FRET), as their emission at 500 nm overlaps with the absorption of the acceptor DOX at 485 nm. NH2-PEG-COOH is conjugated to the outer surface of the FMSN at one end and modified by folic acid at the other, so that the formed mesoporous silica composite has the merits of fluorescence imaging, mesoporous nanostructure for drug loading, receptor-mediated targeting and real-time monitoring of intracellular drug release. It was found that the FA-grafted and PEGlated nanocomposite has excellent biocompatibility towards Hep2 cells, and that the cytotoxicity of the loaded-DOX nanoparticles, containing the folate targeting units in the folate-receptor-rich Hep2 cancer cells, is higher than that without folate targeting units, under the same conditions. When the resultant nanoparticles enter into the cells, the green fluorescence of FMSN gradually recovers along with the release of DOX, to achieve the purpose of real-time monitoring of intracellular drug release.