Rational\nDesign of Conjugated Polymers for Photocatalytic\nCO<sub>2</sub> Reduction: Towards Localized CO Production and Macrophage\nPolarization

Light\npresents substantial potential in disease treatment, where\nthe development of efficient photocatalysts could enhance the utilization\nof photocatalytic systems in biomedicine. Here, we devised a novel\napproach to designing and synthesizing photocatalysts of conjugated\npolymers for photocatalytic CO<sub>2</sub> reduction, relying on a\nmultiple linear regression model built with theoretically calculated\ndescriptors. We established a logarithmic relationship between molecular\nstructure and CO yield and identified the poly(fluorene-<i>co</i>-thiophene) deviant (PFT) as the optimal one. PFT excited a CO regeneration\nratio of 231 nmol h<sup>–1</sup> in acetonitrile and 46 nmol\nh<sup>–1</sup> in an aqueous solution with a reaction selectivity\nof 88%. Further advancements were made through the development of\nliposomes encapsulating PFT for targeted macrophage delivery. By distributing\nPFT on the liposome membranes, our constructed photocatalytic system\nefficiently generated CO in situ from surrounding CO<sub>2</sub>.\nThis localized CO production served as an endogenous signaling molecule,\npromoting the desirable polarization of macrophages from the M1 to\nM2 phenotype. Consequently, the M2 cells reduced the secretion of\npro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). We\nalso demonstrated the efficacy of our system in treating lipopolysaccharide-induced\ninflammation of cardiomyocytes under white light irradiation. Moreover,\nour research provides a comprehensive understanding of the intricate\nprocesses involved in CO<sub>2</sub> reduction by a combination of\ntheoretical calculations and experimental techniques including transient\nabsorption, femtosecond ultrafast spectroscopy, and in situ infrared\nspectroscopy. These findings pave the way for further advancements\nof conjugated polymers and photocatalytic systems in biomedical investigation.