Real-time self-tracking of an anticancer small molecule nanodrug based on colorful fluorescence variations

A new self-tracking nanoscale drug delivery system has been developed to monitor drug delivery and release in tumor cells. The small molecule nanodrug was constructed via the conjugation and self-assembly of two widely used anticancer drugs, hydrophilic irinotecan (Ir) which displays blue fluorescence and hydrophobic doxorubicin (DOX) which displays red fluorescence, which produced colorful fluorescence variations during drug delivery and release in cells. Owing to the fluorescence resonance energy transfer (FRET), the Ir-DOX conjugate emitted strong red fluorescence when excited at a short wavelength. Benefiting from its amphiphilicity, the Ir-DOX conjugate self-assembled into micelles in aqueous medium and the fluorescence was quenched due to aggregation-caused quenching (ACQ). No obvious red or blue fluorescence was observed during a 12 h cell incubation with Ir-DOX, indicating that Ir-DOX entered cells in the form of micelles rather than free conjugate or free drugs. With increasing incubation time, the breaking of the Ir-DOX linkage resulted in the release of both free drugs, leading to the recovery of dual-color fluorescence. In vitro cytotoxicity studies showed that the Ir-DOX micelles could overcome the multidrug resistance (MDR) of tumor cells, resulting in a prominent growth inhibition against cancer cell proliferation. The Ir-DOX small molecule nanodrug provides a new design for real-time self-tracking of carrier-free and probe-free drug delivery systems in cancer treatment.