Rational Design of Conjugated Polymers for Photocatalytic CO2 Reduction: Towards Localized CO Production and Macrophage Polarization.

ABSTRACT

Light presents substantial potential in disease treatment, where the development of efficient photocatalysts could enhance the utilization of photocatalytic systems in biomedicine. Here, we devised a novel approach to designing and synthesizing photocatalysts of conjugated polymers for photocatalytic CO2 reduction, relying on a multiple linear regression model built with theoretically calculated descriptors. We established a logarithmic relationship between molecular structure and CO yield and identified the poly(fluorene-co-thiophene) deviant (PFT) as the optimal one. PFT excited a CO regeneration ratio of 231 nmol h-1 in acetonitrile and 46 nmol h-1 in an aqueous solution with a reaction selectivity of 88%. Further advancements were made through the development of liposomes encapsulating PFT for targeted macrophage delivery. By distributing PFT on the liposome membranes, our constructed photocatalytic system efficiently generated CO in situ from surrounding CO2. This localized CO production served as an endogenous signaling molecule, promoting the desirable polarization of macrophages from the M1 to M2 phenotype. Consequently, the M2 cells reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß). We also demonstrated the efficacy of our system in treating lipopolysaccharide-induced inflammation of cardiomyocytes under white light irradiation. Moreover, our research provides a comprehensive understanding of the intricate processes involved in CO2 reduction by a combination of theoretical calculations and experimental techniques including transient absorption, femtosecond ultrafast spectroscopy, and in situ infrared spectroscopy. These findings pave the way for further advancements of conjugated polymers and photocatalytic systems in biomedical investigation.