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

ABSTRACT 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 ( 1 O 2 ) release triggered by H 2 O 2 during therapy phase. However, its inherent uncontrolled release characteristics reduce therapeutic precision and safety. Herein, a conjugate BTMI‐PyB was constructed to store 1 O 2 via dynamic boronic ester bonds. Upon light irradiation, BTMIs‐PyB underwent a “ self‐charging ” process utilizing the 1 O 2 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 H 2 O 2 in the tumor microenvironment to release 1 O 2 . 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.