Nanostructured Phthalocyanine Assemblies with Efficient Synergistic Effect of Type I Photoreaction and Photothermal Action to Overcome Tumor Hypoxia in Photodynamic Therapy

• DOI: 10.1021/jacs.1c07479
• Publication Date: 2021-08-24T05:10:20Z
• Authors: Yuan-Yuan Zhao; Ling Zhang; Zixuan Chen; Bi-Yuan Zheng; Meirong Ke; Xingshu Li; Jian-Dong Huang
• Keywords: Photosensitizing Agents; Light; Singlet Oxygen; Cell Survival; Optical Imaging; Transplantation, Heterologous; Isoindoles; 01 natural sciences; Cell Hypoxia; Nanostructures; 0104 chemical sciences; 3. Good health; Mice; Photochemotherapy; Cell Line, Tumor; Drug Design; Neoplasms; Animals; Humans

Most photodynamic therapy (PDT) paradigms work through the highly O2-dependent type II photoreaction to generate singlet oxygen (1O2). The hypoxic microenvironment of solid tumors severely hampers therapeutic outcomes. Here, we present a novel design that could transfer the photophysical and photochemical properties of traditional phthalocyanine-based photosensitizers from type II photoreaction to efficient type I photoreaction and vibrational relaxation-induced photothermal conversion. These features enable the obtained nanostructured phthalocyanine assemblies (e.g., NanoPcAF) to display excellent phototherapies under both normoxic and hypoxic conditions. Moreover, NanoPcAF has a high level of accumulation in tumor tissues after intravenous injection, and 94% of tumor growth is inhibited in a preclinical model at a NanoPcAF dose of 0.8 nmol g-1 and light dose of 300 J cm-2.