Shao Wei, Yang Chuang, Li Fangyuan, Wu Jiahe, Wang Nan, Ding Qiang, Gao Jianqing, Ling Daishun
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.
Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
Nanomicro Lett. 2020 Jul 13;12(1):147. doi: 10.1007/s40820-020-00474-6.
Simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) is beneficial for enhanced cancer therapy due to the synergistic effect. Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources. The emerging monocomponent diketopyrrolopyrrole (DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation, but suffer from low singlet oxygen quantum yield, which severely restricts the therapeutic efficacy. Herein, we report acceptor-oriented molecular design of a donor-acceptor-donor (D-A-D) conjugated small molecule (IID-ThTPA)-based phototheranostic agent, with isoindigo (IID) as selective acceptor and triphenylamine (TPA) as donor. The strong D-A strength and narrow singlet-triplet energy gap endow IID-ThTPA nanoparticles (IID-ThTPA NPs) high mass extinction coefficient (18.2 L g cm), competitive photothermal conversion efficiency (35.4%), and a dramatically enhanced singlet oxygen quantum yield (84.0%) comparing with previously reported monocomponent PTT/PDT agents. Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.
由于协同效应，同步光热疗法（PTT）和光动力疗法（PDT）对增强癌症治疗有益。为协同PTT/PDT开发的传统材料通常是多组分试剂，需要复杂的制备程序并由多个激光源激活。新兴的基于单组分二酮吡咯并吡咯（DPP）的共轭小分子试剂能够在单一激光照射下实现双PTT/PDT，但单线态氧量子产率较低，这严重限制了治疗效果。在此，我们报告了一种基于供体-受体-供体（D-A-D）共轭小分子（IID-ThTPA）的光诊疗剂的受体导向分子设计，其中异吲哚啉酮（IID）作为选择性受体，三苯胺（TPA）作为供体。与先前报道的单组分PTT/PDT试剂相比，强D-A强度和窄的单重态-三重态能隙赋予IID-ThTPA纳米颗粒（IID-ThTPA NPs）高质量消光系数（18.2 L g cm）、有竞争力的光热转换效率（35.4%）和显著提高的单线态氧量子产率（84.0%）。IID-ThTPA NPs如此高的PTT/PDT性能在体外和体内均实现了卓越的肿瘤协同根除能力。
