(173h) Tuning C-Phycocyanin Photoactivity Via pH-Mediated Assembly–Disassembly
AIChE Annual Meeting
2022
2022 Annual Meeting
Poster Sessions
General Poster Session
Monday, November 14, 2022 - 3:30pm to 5:00pm
C-phycocyanin (C-PC), a major proteinâchromophore complex originating in cyanobacteria and red algae, is characterized by hierarchical protein architecture and unique light-sensing ability. Using small-angle X-ray scattering, a pH-mediated assemblyâdisassembly pathway of C-PC in solution state was unraveled. With pH changes in the 3.0â9.0 range, the partially unfolded monomers found in both acidic (pH 3.0) and alkaline (pH 9.0) conditions can be converted to the well-folded trimers at pH 7.0 and high assembliesâa mixture of trimers, hexamers, and nonamersâat pH 5.0. Such flexible protein matrices impart tunability to the embedded tetrapyrroles, whose photochemical behaviors were found to be modulated by protein assembly states. 365-nm UV irradiation on C-PC triggers pH-dependent singlet oxygen (1O2) generation and conformational changes. Intermolecular photo-crosslinking occurs at pH 5.0 via dityrosine species, which bridges solution-based C-PC oligomers into unprecedented dodecamers and 24-mers. These supramolecular assemblies impart C-PC at pH 5.0 significantly enhanced 1O2 yield, fluorescence emission, and photostability relative to those at other pH values.
The identified pH tunability via proteinâchromophore ineractions makes C-PC a potential pH-responsive photosensizer for tumor-targeted photodynamic therapy. The enhanced activation of C-PC in weakly acidic environments (pH 5.0) makes C-PC a potential pH-responsive photosensizer for tumor-targeted photodynamic therapy as tumor microenvironments, for example, the lysosome (pH ~4.5â5.0), are characterized by similar acidity. In this sense, C-PC could be utilized in the design of novel pH-responsive fluorescent imaging probes or 1O2 generators to boost photodynamic activities at acidic tumor sites while minimizing phototoxicity to non-target healthy tissues. It is envisaged that with further development, the remarkable pH-responsiveness, photoactivity, and conformational flexibility of C-PC demonstrated in this work, along with this proteinâs inherent biocompatibility and wide availability, will open new routes for its applications in cancer diagnosis, imaging, and photodynamic therapy (PDT).