Water‐Soluble Self‐Assembled Radical Nanoparticles for Deep‐Red Fluorescence‐Guided Type I/II Photodynamic Therapy

ABSTRACT Organic luminescent radicals with efficient doublet emission can directly transfer electrons and energy to oxygen, enabling fluorescence‐guided photodynamic therapy. However, their water insolubility and unclear oxygen interaction mechanisms limit their application. To address these challenges, we synthesized an amphiphilic organic radical (TTM‐2PyPh) that forms self‐assembled water‐soluble nanoparticles (TTM‐2PyPh_SA@NPs) with deep‐red emission, serving as Type‐I/II photosensitizers. Quantum chemistry calculations confirm an efficient electron transfer process between the radicals and oxygen. These nanoparticles self‐assemble in vivo, target tumors, and produce reactive oxygen species more effectively than core‐shell nanoparticles (TTM‐2Py_CS@NPs), chlorin e6, and methylene blue. Additionally, TTM‐2PyPh_SA@NPs demonstrate superior tumor eradication in vivo. This work advances the development of novel water‐soluble radical‐based photosensitizers for enhanced photodynamic therapy.