Smart on-off-on fluorescent switches for drug visual loading and responsive delivery

The unsatisfactory therapeutic effects and limitations of chemotherapy are urging people to find more effective therapy methods, and drug delivery systems have been attracting increasing research interests. However, most of these studies mainly focused on the therapeutic effects, while little attention was paid to explore new drug loading patterns and improve the efficiency. Herein, a pair of smart on-off-on fluorescent switches based on a novel double fluorescence resonance energy transfer (FRET) system was established to realize facilely visual drug loading and responsive delivery. To build this nanosystem, highly luminescent carbon quantum dots (CQDs) were first prepared and further loaded by anticancer drugs of doxorubicin (DOX). The pi-pi and hydrogenbonding interactions between them readily formed the first FRET system, which allowed to facilely monitor the drug loading process by detecting the solution color changes with naked eyes. Then, manganese dioxide (MnO2) with high surface area, further modified by polydopamine and folic acid was synthesized and served as the other FRET receptor for CQDs and DOX, facilitating monitor of full drug absorption and loading by total fluorescence quenching. Moreover, when the double-FRET nanosystem was endocytosed into cancer cells, MnO2 was responsively degraded into Mn2+ under intracellular glutathione and acid conditions, which resulted into sustained drug release and gradual fluorescence recovery. More importantly, the constructed nano-system also exhibited selectively drug delivery and showed much finer therapeutic effects than single chemotherapy, holding great potential in future cancer therapy.