FRET-Modulated Fluorescence Lifetime-Traceable Nanocarriers for Multidrug Release Monitoring and Synergistic Therapy.

In situ monitoring multidrug release in complex cellular microenvironments is significant, and currently, it is still a great challenge. In this work, a smart nanocarrier with the capability of codelivery of small molecules and gene materials as well as with Förster resonance energy transfer (FRET)-modulated fluorescence lifetime is fabricated by integrating gold nanoparticles (the acceptor) into dual-mesoporous silica loaded with multiple drugs (the donor). Once internalized into tumor cells, in weakly acidic environments, the conformation switch of the polymer grafted on nanocarriers causes its shedding from the mesopores, triggering the release of drugs. Simultaneously, based on the strong overlap between the emission spectrum of donors and the absorption spectrum of the acceptors, any slight fluctuation of the dissociation of the drugs from nanocarriers can result in a change in the FRET-modulated lifetime signal due to the extraordinarily sensitive FRET signal to the separation distance between donors and acceptors. All these implied the potential applications of this nanoplatform in various biomedical fields that require the codelivery and real-time monitoring of multidrug-based synergistic therapy.