AIE Institute, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
Department of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Biomaterials. 2022 Jan;280:121255. doi: 10.1016/j.biomaterials.2021.121255. Epub 2021 Nov 17.
The pursuing of photosensitizers (PSs) with efficient reactive oxygen species (ROS) especially type I ROS generation in aggregate is always in high demand for photodynamic therapy (PDT) and photoimmunotherapy but remains to be a big challenge. Herein, we report a cationization molecular engineering strategy to boost both singlet oxygen and radical generation for PDT. Cationization could convert the neutral donor-acceptor (D-A) typed molecules with the dicyanoisophorone-triphenylamine core (DTPAN, DTPAPy) to their A-D-A' typed cationic counterparts (DTPANPF and DTPAPyPF). Our experiment and simulation results reveal that such cationization could enhance the aggregation-induced emission (AIE) feature, promote the intersystem crossing (ISC) processes, and increase the charge transfer and separation ability, all of which work collaboratively to promote the efficient generation of ROS especially hydroxyl and superoxide radicals in aggregates. Moreover, these cationic AIE PSs also possess specific cancer cell mitochondrial targeting capability, which could further promote the PDT efficacy both in vitro and in vivo. Therefore, we expect this delicate molecular design represents an attractive paradigm to guide the design of type I AIE PSs for the further development of PDT.
寻求具有高效活性氧（ROS）特别是 I 型 ROS 生成能力的光敏剂一直是光动力疗法（PDT）和光免疫疗法的迫切需求，但这仍然是一个巨大的挑战。在此，我们报告了一种阳离子化分子工程策略，以增强 PDT 中的单线态氧和自由基生成。阳离子化可以将具有二氰基异佛尔酮-三苯胺核（DTPAN，DTPAPy）的中性给体-受体（D-A）型分子转化为其 A-D-A'型阳离子对应物（DTPANPF 和 DTPAPyPF）。我们的实验和模拟结果表明，这种阳离子化可以增强聚集诱导发射（AIE）特性，促进系间窜越（ISC）过程，并增加电荷转移和分离能力，所有这些都协同作用，促进 ROS 的有效生成，特别是在聚集物中生成羟基和超氧自由基。此外，这些阳离子 AIE PS 还具有特定的癌细胞线粒体靶向能力，这可以进一步提高体外和体内的 PDT 疗效。因此，我们期望这种精细的分子设计代表了一种有吸引力的范例，可以指导 I 型 AIE PS 的设计，以进一步发展 PDT。
