A combination of covalent and noncovalent restricted-intramolecular-rotation strategy for supramolecular AIE-type photosensitizer toward photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a promising noninvasive method for targeted cancer cell destruction. Still, its effectiveness is often hindered by the aggregation-caused quenching effect of organic photosensitizer (PS) in aqueous environments. Here, we have employed a combination of covalent and noncovalent restricted-intramolecularrotation strategies to develop supramolecular PSs with aggregation-induced emission (AIE) characteristics. Firstly, a water-soluble octacationic molecular cage (1) with a bilayer tetraphenylethene (TPE) structure has been designed and synthesized, which minimizes intramolecular rotation of TPE moieties and achieves the single-molecule-level aggregation by the covalent restriction of intramolecular rotation (RIR) via molecular engineering synthesis. Compared with its single-layer TPE analog, 1 exhibits superior efficiency in generating reactive oxygen species (ROS) including superoxide radical (O2^–•) and singlet oxygen (1O2) upon whitelight irradiation. Subsequently, by forming a 1:4 host–guest complex (1@CB[8]₄) between 1 and cucurbit[8]uril (CB[8]), O₂^–• generation can be further enhanced by the noncovalent RIR via the host–guest assembly. Additionally, 1@CB[8]₄ as a photocatalyst promotes rapid oxidation of nicotinamide adenine dinucleotide (NADH) in water. Given its Type-I ROS generation and catalytic activity for NADH oxidation, 1@CB[8]₄ acts as a supramolecular AIE-type PS to exhibit strong photo-induced cytotoxicity upon white-light irradiation under hypoxic conditions, showcasing its potential for synergistic PDT.

Keywords

aggregation-induced emission / cage compounds / cucurbit[8]uril / photodynamic therapy / supramolecular photosensitizer

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2024 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.