Abstract：
The spin-orbit charge transfer intersystem crossing (SOCT-ISC) photophysical process has shown great potential for constructing heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) of tumors. However, for almost all such PSs reported to date, the SOCT-ISC is driven by the acceptor-excited photoinduced electron transfer (a-PeT). In this work, for the first time the donor-excited photoinduced electron transfer (d-PeT)-driven SOCT-ISC mechanism is utilized to construct the heavy-atom-free PSs for PDT of tumors by directly installing the electron-deficient N-alkylquinolinium unit (as an electron acceptor) into the meso-position of the near-infrared (NIR) distyryl Bodipy chromophore (as an electron donor). In the less polar environment, the PSs exist as the monomer and promote the production of singlet oxygen (1O2) (Type-II) relying on the d-PeT-driven population of the triplet excited state via SOCT-ISC, whereas in the aqueous environment, they exist as nanoaggregates and induce the generation of superoxides (O2-•) and hydroxyl radicals (HO•) (Type-I) via the d-PeT-driven formation of the delocalized charge-separated state. The PSs could rapidly be internalized into cancer cells and induce the simultaneous production of intracellular 1O2, O2-•, and HO• upon NIR light irradiation, endowing the PSs with superb photocytotoxicity with IC50 values up to submicromolar levels whether under normoxia or under hypoxia. Based on the PSs platform, a tumor-targetable PS is developed, and its abilities in killing cancer cells and in ablating tumors without damage to normal cells/tissues under NIR light irradiation are verified in vitro and in vivo. The study expands the design scope of PSs by introducing the d-PeT conception, thus being highly valuable for achieving novel PSs in the realm of tumor PDT.
摘要：
自旋轨道电荷转移系统间交叉（SOCT-ISC）光物理过程在构建用于肿瘤光动力治疗（PDT）的无重原子光敏剂（PS）方面显示出巨大的潜力。然而,对于迄今为止报道的几乎所有这样的PS，SOCT-ISC由受体激发的光诱导电子转移(a-PeT)驱动。在这项工作中,首次利用供体激发的光诱导电子转移（d-PeT）驱动的SOCT-ISC机制，通过直接将缺电子的N-烷基喹啉单位（作为电子受体）安装到近红外（NIR）二苯乙烯基Bodippy发色团（作为电子供体）的中观位置来构建用于肿瘤PDT的无重原子PSs。在极性较低的环境中，PSs作为单体存在，并通过SOCT-ISC促进单线态氧（1O2）（II型）的产生，依赖于三重态激发态的d-PeT驱动种群，而在水性环境中，它们以纳米聚集体的形式存在，并通过d-PeT驱动的离域电荷分离状态的形成诱导超氧化物（O2-•）和羟基自由基（HO•）（I型）的产生。PS可以迅速内化到癌细胞中，并诱导细胞内同时产生1O2，O2-•，和HO•在NIR光照射下，无论在常氧下还是在低氧下，均赋予PSs极好的光细胞毒性，IC50值高达亚微摩尔水平。基于PS平台，开发了一种可靶向肿瘤的PS，在体外和体内验证了其在NIR光照射下杀死癌细胞和消融肿瘤而不损害正常细胞/组织的能力。本研究通过引入d-PeT概念，扩大了PS的设计范围，因此对于在肿瘤PDT领域实现新型PS非常有价值。
