A CD206-Targeted Singlet-Oxygen Battery for Type I/II Photodynamic Therapy of Deep-Seated Colorectal Cancer.

The efficacy of conventional photodynamic therapy (PDT) is severely constrained by the hypoxic tumor microenvironment and limited light penetration depth, particularly for deep-seated colorectal cancer (CRC). The singlet oxygen battery (SOB) offers a promising approach to circumvent these limitations by realizing oxygen- and light-independent singlet oxygen (1O2) release triggered by H2O2 during therapy phase. However, its inherent uncontrolled release characteristics reduce therapeutic precision and safety. Herein, a conjugate BTMI-PyB was constructed to store 1O2 via dynamic boronic ester bonds. Upon light irradiation, BTMIs-PyB underwent a "self-charging" process utilizing the 1O2 generated by BTMIs to yield BTMIs-PyOB. Notably, the resulting intelligent nanosystem could achieve targeted delivery to colon cancer cells by leveraging the specific recognition between mannose and the CD206 receptor. Experiments on 2D cells, 3D cell spheres and tumor bearing mice demonstrated that BTMIs-PyOB could induce CT26 cell death through highly efficient type I/II PDT upon light irradiation. Moreover, under dark and hypoxic conditions, BTMIs-PyOB could be activated by overexpressed H2O2 in the tumor microenvironment to release 1O2. This advancement breaks through the dependence of traditional PDT on light and oxygen, providing a novel therapeutic strategy for the treatment of deep-seated tumors by integrating conventional PDT with stimulus-responsive therapy.