The aggregation-induced enhanced photosensitization and emission (AIEPE) properties of spiropyrans in nanoassemblies enable reversibly controlled singlet oxygen generation.

Water-soluble conjugated polymers (WCPs) have prospective applications in the field of bioimaging, disease diagnosis, and therapy. However, the use of WCPs with controllability and regioregularity for bioapplications have scarcely been reported. In this work, we synthesized polythiophenes containing ester side chains (P3ET) via Kumada catalyst-transfer polycondensation (KCTP) and confirmed a quasi-"living" chain-growth mechanism. In addition, we obtained cationic regioregular polythiophenes (cPTs) by aminolysis of P3ET with varied chain lengths, and studied DNA binding capability and gene delivery performance. Benefiting from photocontrolled generation of intracellular reactive oxygen species (ROS), the cationic polythiophenes successfully delivered DNA into tumor cells without additional polymer species.

Conjugated polymers can serve as good photosensitizers in biomedical applications. However, it remains unknown whether they are phototoxic to the supercoiled structure of DNA in improving gene delivery by the photochemical internalization (PCI) strategy, which complicates the application of conjugated polymers in gene delivery. In this work, we introduced a trace amount of cationic poly(phenylene ethynylene)s (cPPEs) into the polymeric shell of branched polyethylenimine (BPEI)/DNA complexes, studied the photosensitization of singlet oxygen by cPPEs, and confirmed that the supercoiled DNA is undamaged by the singlet oxygen generated by the photoexcitation of cPPEs. By taking advantage of the cPPE-mediated PCI effect, we report that the addition of the trace amount of cPPEs to the outer shell of the BPEI/DNA polyplexes could greatly amplify the transfection of gene green fluorescent protein on tumor cells with the efficiency from 14 to 86% without decreasing the cell viabilities, well solving the problem with a poor transfection capability of BPEI under low DNA-loading conditions. Our strategy to employ conjugated polymers as photosensitizing agents in gene delivery systems is simple, safe, efficient, and promising for broad applications in gene delivery areas.

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