Comparing Effects of Redox Sensitivity of Organic Nanoparticles to Photodynamic Activity

Smart responsive nanomaterials, which are sensitive to biological signals, are promising therapeutic formulations. It has been well studied that redox potential is much different at both tissue and cellular level. In this work, three organic nanoparticles with variable redox sensitivity were fabricated, and their redox sensitivity was evaluated and compared in detail. First, diselenide, disulfide, and carbon–carbon bond containing porphyrin dimers TPP-SeSe/TPP-SS/TPP-CC were synthesized. Then, the corresponding self-assembled nanoparticles (TPP-SeSe/TPP-SS/TPP-CC NPs) were prepared via nanoprecipitation method. As-synthesized nanoparticles were utilized to systematically compare the stimuli responsiveness to reductive agents (e.g., glutathione) in different conditions, especially in the living cells, through the singlet oxygen generation ability and the cytotoxicity. A series of experimental results demonstrated that the diselenide bond shows better superiority in reduction sensitivity than that of the disulfide or carbon–carbon bond, which contributed to faster delivery of the photosensitizer and facilitated exertion of better PDT activity. These results highlight the potential of the diselenide bond to be developed as a novel and effective platform to fabricate more functional stimuli-responsive nanomaterials.