Molecular engineering of tetraphenylethene/thiophene-based donor/π-bridge units to enhance the AIE effect and boost the oxygen-independent type-I ROS generation

The development of oxygen-independent type-I photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics is highly in demand to treat hypoxic tumors but remains challenging. In this contribution, three anion-π+ AIE-PSs (TPEMA-SI, TPEMA-SSI, and TPETPA-SSI) with strong donor-π-acceptor (D-π-A) configurations were facially synthesized by modulating donor/π-bridge units. The strength of D-π-A configurations as well as the AIE-effect that collectively promotes the intersystem crossing (ISC) for boosting the type-I ROS could be enhanced significantly by tuning the electronic characters of D/π-bridge units. The anion-π+ AIE-PSs, with strong D-π-A configurations and heavy atom effect, produced a mixture of type-I as well as type-II ROS. Among them, TPETPA-SSI, with strong D-π-A configuration as well as greater AIE-effect, demonstrated superior type-I ROS generation efficiency. The biocompatible nanoparticles of anion-π+ AIE-PSs (AIE-PSs NPs) were fabricated after being encapsulated into an amphiphilic polymer (DSPE-PEG). The TPETPA-SSI NPs with superior ROS generation efficiency, demonstrate efficient PDT effects towards MCF-7 and U87MG cancer cells in both normoxia and hypoxia environments. This study provides insights into the design and development of type-I AIE-PSs by enhancing the strength of D-π-A configurations and the AIE effect.