Targeted photodynamic therapy using a water-soluble aggregation-Induced emission photosensitizer activated by an acidic tumor microenvironment

Abstract

• A high-efficiency procedure to prepare water-soluble AIE PS with high selectivity was developed for tumor treatment. • The obtained water-soluble AIE PS has a remarkable D-A structure and a low ΔE st value of 0.2 eV. • The system was constructed through supramolecular assembly and activated by the acidic tumor microenvironment. • The host–guest complex might become a precision medicine for the clinic application of PDT. Aggregation-induced emission (AIE)-active photosensitizers (PSs) are considered as a kind of promising functionalized materials for photodynamic therapy of tumor. Improving the targeted ability of water-soluble AIE PSs capable of minimizing the inadvertent activation is of great significance but remains a challenging task. Herein, we report an effective synthetic strategy for preparing water-soluble AIE photosensitizer (termed WAPS) with high targeted capacity mediated by supramolecular assembly. The pillar [5] arene (WP5) can bind WAPS through host–guest interaction in neutral aqueous solution, resulting in a large change in donor–acceptor structure of WAPS and a weak photodynamic activity. Notably, the binding interface of WAPS and WP5 shifts under an acidic environment (pH 5.2), permitting the reversible control of singlet oxygen ( 1 O 2 ) generation and photodynamic targeting of cancer cells in cultured and tumor-bearing mice. This work provides an ingenious way to prepare water-soluble AIE PS with high selectivity for tumor treatment.