Covalent Organic Polymers Based on Fluorinated Porphyrin as Oxygen Nanoshuttles for Tumor Hypoxia Relief and Enhanced Photodynamic Therapy

Effective and sustained tumor oxygenation has found practical significance in benefiting the treatment of solid tumors. In this study, fluorinated covalent organic polymers (COPs) are prepared by cross‐linking the photosensitizer meso‐5, 10, 15, 20‐tetra (4‐hydroxylphenyl) porphyrin (THPP) with perfluorosebacic acid (PFSEA) and poly(ethylene glycol) (PEG) via a one‐pot esterification, to enable simultaneous tumor oxygenation and photodynamic treatment. Due to the presence of PFSEA, the obtained THPP pf –PEG shows efficient loading of perfluoro‐15‐crown‐5‐ether (PFCE), a type of perfluocarbon, and thereby molecular oxygen, both of which would significantly enhance the photodynamic effect of THPP. After chelating THPP with a radio‐isotope, 99m Tc, both THPP pf –PEG and PFCE‐loaded THPP pf –PEG (PFCE@THPP pf –PEG) can be vividly visualized under the single‐photon emission computed tomography (SPECT) imaging, which uncovers efficient tumor accumulation of those COPs' post intravenous injection. Owing to the oxygen delivery ability of PFCE, efficient tumor oxygenation is observed for mice post injection of PFCE@THPP pf –PEG, which further leads to greatly enhanced photodynamic treatment of tumors. This study presents a unique type of multifunctional fluorinated COPs with well‐defined composition, long blood circulation time, and sustained tumor oxygenation ability, showing great promises for potential clinical translation in photodynamic treatment of tumors.