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

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.