Recently, the research work of Prof. Zhu Weihong group, titled "In Vivo and in Situ Tracking Cancer Chemotherapy by Highly Photostable NIR Fluorescent Theranostic Prodrug" is published on Journal of the American Chemical Society  (J.Am. Chem. Soc., 2014, 136, 3579−3588).

    In vivo monitoring of the biodistribution and activation of prodrugs for cancer therapy is urgently required. Controllable fluorescent drug delivery system (FDDS) is one of the most promising strategies for tracking prodrugs upon in vivo uptaking. However, the current FDDS for drug release performance is indirectly predicted via in vitro experiments because their fluorophores suffer from short wavelength emission. W.Zhu and Z. Guo at East China University of Science and Technology (Shanghai), J. Tang at Zhejiang University (Hangzhou) and co-workers smartly developed a near-infrared (NIR) fluorescent theranostic prodrug, especially realizing in vivo and in situ tracking of drug release and cancer therapeutic efficacy in mice.

    To make this prodrug, a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorophore was conjugated with camptothecin (CPT) as the anticancer drug using a disulfide linker. As a control system,  an uncleavable linker was employed in DCM-C-CPT. In vitro experiments verify that, only the disulfide linker in DCM-S-CPT is cleaved by the high intracellular glutathione (GSH) concentrations in tumor cells, concomitantly resulting in the active drug CPT release and significant turn-on NIR fluorescence with large Stokes shift (200 nm). The researchers has well demonstrated that  DCM-S-CPT and its loaded in PEG-PLA nanoparticles exhibits excellent tumor-activatable performance when intravenously injected into tumor-bearing nude mice, as well as specific cancer therapy with little side effects.

    Particularly, DCM-S-CPT possesses fantastic photo-stability with respect to commercial cyanine dye ICG (the FDA-approved NIR contrast agent). This work presents an excellent example of photostable NIR promising prodrug with good tumor-targeting ability, highly beneficial for deeper understanding and exploration of theranostic drug-delivery systems.

    Related Links：http://pubs.acs.org/doi/abs/10.1021/ja412380j