Protein-Activatable Diarylethene Monomer as a Smart Trigger of Noninvasive Control Over Reversible Generation of Singlet Oxygen: A Facile, Switchable, Theranostic Strategy for Photodynamic-Immunotherapy

The development of activatable photosensitizers to allow for the reversible control of singlet oxygen (¹O₂) production for photodynamic therapy (PDT) faces great challenges. Fortunately, the flourishing field of supramolecular biotechnology provides more effective strategies for activatable PDT systems. Here, we developed a new reversible PDT on a switch that controls the ¹O₂ generation of self-assembled albumin nanotheranostics in vitro and in vivo. A new molecular design principle of aggregation-induced self-quenching photochromism and albumin on-photoswitching was demonstrated using a new asymmetric, synthetic diarylethene moiety <b>DIA</b>. The photosensitizer porphyrin and <b>DIA</b> were incorporated as building blocks in a glutaraldehyde-induced covalent albumin cross-linking nanoplatform, <b>HSA-DIA-porphyrin nanoparticles</b> (NPs). More importantly, the excellent photoswitching property of <b>DIA</b> enables the resultant nanoplatform to act as a facile, switchable strategy for photodynamic-immunotherapy.