Activatable phototheranostics is highly appealing to meet the demand of precision medicine, where the photosensitizer is selectively switched on in the lesion microenvironment or inside the diseased cells by responding to the biological stimulus, and stays inert during its systemic circulation. Our group proposed a novel concept of biomarker displacement activation (BDA), which can be achieved by using host-guest strategy and realizes supramolecular phototheranostics. In BDA, a photosensitizer is preloaded into the cavity of a receptor with the fluorescence and photoactivity annihilated (OFF state); when encountering a biomarker which is overexpressed in diseased tissues, the competitive inclusion of the biomarker gives rise to the release of the photosensitizer, accompanied by the recovery of fluorescence and photoactivity (ON state). The BDA strategy provides the following advantages: (1) employment of approved photosensitizers without custom covalent decoration, (2) traceless release of the photosensitizers with high fidelity by biomarker displacement, (3) adaptability to different photosensitizers for establishing a universal platform and promised facile combination of diverse photosensitizers to enhance photon utility in light window.

Adenosine triphosphate (ATP) severely overexpressed in tumor tissues than in normal tissues. Taking ATP as the biomarker, a BDA platform was engineered using the pegylated amphiphilic guanidinocalix[5]arene nanocarrier. The general phototheranostics nanoplatform is adaptive to various anionic photosensitizers which are commercially available. More importantly, the self-assembled nanosystem is of dual selectivity for tumor-targeted phototheranostics in vivo that results from the enhanced permeability and retention effect and tumor-ATP response. Compared with free photosensitizer, the photosensitizer/guanidinocalix[5]arene nanoparticle is not only able to selectively visualize tumor in real time, but also gives rise to much more efficient cancer ablation. To be envisaged, this concept of BDA is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged. (J. Am. Chem. Soc., 2018, 140, 4945–4953, collaborated with Prof. Dan Ding)