Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics

↵‡ Present address: Institute of Translational Medicine, The First Hospital; State Key Laboratory of Supramolecular Structure and Materials College of Chemistry, Jilin University, Changchun 130021, China. NIR-II fluorescence imaging greatly reduces scattering coefficients for nearly all tissue types at long wavelengths, benefiting deep tissue imaging. However, most of the NIR-II fluorophores suffer from low quantum yields and/or short circulation time that limit the quality of NIR-II imaging. Here, we engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a NIR-II quantum yield of 21.2% with prolonged circulation time. Computational modeling revealed the mechanism for fluorescence enhancement and identified key parameters governing albumin complex for NIR-II fluorophores. Our complex afforded high-resolution microvessel imaging, with a 3-hour imaging window compared to 2 min for free dye alone. Furthermore, the complexation strategy was applied to an antibody-derived assembly, offering high-contrast tumor imaging without affecting the targeting ability of the antibody. This study provides a facile str...

How cardiolipin modulates the dynamics of respiratory complex I

Cardiolipin modulates the activity of membrane-bound respiratory enzymes that catalyze biological energy transduction. The respiratory complex I functions as the primary redox-driven proton pump in mitochondrial and bacterial respiratory chains, and its activity is strongly enhanced by cardiolipin. However, despite recent advances in the structural biology of complex I, cardiolipin-specific interaction mechanisms currently remain unknown. On the basis of millisecond molecular simulations, we suggest that cardiolipin binds to proton-pumping subunits of complex I and induces global conformational changes that modulate the accessibility of the quinone substrate to the enzyme. Our findings provide key information on the coupling between complex I dynamics and activity and suggest how biological membranes modulate the structure and activity of proteins. Complex I (NADH:ubiquinone oxidoreductase) functions as a redox-driven proton pump in aerobic respiratory chains (1–3). With a molecular mass of ca. 1 MDa distributed among up to 45 subunits in eukaryotes (4–7), complex I is the largest, most intricate, and least understood enzyme of the respiratory chain. The over 100-Å-long hydrophi...