Biomarker Displacement Activation: A General Host-Guest Strategy for Targeted Phototheranostics in Vivo.

Abstract

Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although it displays efficacy in the construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes, and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state). When nanocarriers were accumulated into tumor tissues via the enhanced permeability and retention effect, the overexpressed biomarker adenosine triphosphates displaced PSs, accompanied by their fluorescence and photoactivity recovered (ON state). These reinstallations are unattainable in normal tissues, allowing us to concurrently achieve selective tumor imaging and targeted therapy in vivo. Compared with widely used covalent approach, the present BDA strategy provides the following advantages: (1) employment of approved PSs without custom covalent decoration; (2) traceless release of PSs with high fidelity by biomarker displacement; (3) adaptability to different PSs for establishing a universal platform and promised facile combination of diverse PSs to enhance photon utility in light window. Such a host-guest BDA strategy is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.

• Authors: Jie Gao, Jun Li, Wen-Chao Geng, Fang-Yuan Chen, Xingchen Duan, Zhe Zheng, Dan Ding, Dong-Sheng Guo
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 140 Issue 14 Pg. 4945-4953 (04 11 2018) ISSN: 1520-5126 [Electronic] United States
• PMID: 29562139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)