Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Acta Biomater. 2021 Aug;130:447-459. doi: 10.1016/j.actbio.2021.05.048. Epub 2021 May 31.
Owing to their reversibly dynamic features, and the regularity of their architectures, supramolecular organic frameworks (SOFs) have attracted attention as new porous materials. Herein, we propose a smart SOF platform for enhanced photodynamic therapy, where the SOF with a superior mitochondria-targeting capability could be cleaved by reactive oxygen species (ROS) produced by itself for highly enhancing PDT. Moreover, it can further work as a platform for carrying chemo-therapeutic drug doxorubicin for synergistic chemo-photodynamic therapy. The SOF is constructed by combining a tetra-β-cyclodextrin-conjugated porphyrin photosensitizer and a ROS-sensitive thioketal linked adamantane dimer utilizing a host-guest supramolecular strategy. The unique supramolecular framework not only completely resolves the aggregation caused quenching of porphyrin photosensitizers but also endows them with significantly enhanced water-solubility. The in vitro and in vivo results demonstrate that the SOF could be targeted onto mitochondria by confocal imaging, and dissociated by ROS generated by itself, leading to autonomous release of porphyrin photosensitizers and DOX for high anti-cancer activity. It is believed that the strategy using a SOF has the potential of being used to construct versatile agents for combined therapies. STATEMENT OF SIGNIFICANCE: Photosensitizers are the essential element in photodynamic therapy. However, typical photosensitizers commonly encounter poor water-solubility, non-specific tumor-targeting, aggregation-caused quenching (ACQ), which seriously reduce PDT efficacy. A mitochondria-targeting and ROS-sensitive supramolecular organic framework (SOF) is designed for photodynamic therapy in cancer treatment, which could completely overcome the bottleneck in the applications of photosensitizers (PSs). The SOF is constructed by combining a tetra-β-cyclodextrin-conjugated porphyrin photosensitizer and a ROS-sensitive thioketal linked adamantane dimer unit utilizing a host-guest supramolecular strategy. The unique supramolecular framework not only completely resolves the aggregation caused quenching of porphyrin photosensitizers but also endows them with significantly enhanced water-solubility. Moreover, the SOF can be readily functionalized to incorporate the anti-cancer agent Doxorubicin and mitochondria targeting molecules through respective physical encapsulation and host-guest interactions.
由于其可逆动态特性和结构的规则性，超分子有机骨架（SOF）作为新型多孔材料引起了人们的关注。在此，我们提出了一种用于增强光动力疗法的智能 SOF 平台，其中具有优异的靶向线粒体能力的 SOF 可以被自身产生的活性氧（ROS）切割，从而高度增强 PDT。此外，它可以进一步用作携带化疗药物阿霉素的平台，用于协同化疗-光动力疗法。SOF 是通过结合四-β-环糊精-卟啉光敏剂和利用主体-客体超分子策略连接的 ROS 敏感硫代缩酮连接的金刚烷二聚体来构建的。独特的超分子骨架不仅完全解决了卟啉光敏剂的聚集猝灭问题，而且还赋予它们显著增强的水溶性。体外和体内结果表明，SOF 可以通过共聚焦成像靶向线粒体，并通过自身产生的 ROS 解离，导致卟啉光敏剂和 DOX 的自主释放，从而实现高抗癌活性。我们相信，使用 SOF 的策略有可能用于构建用于联合治疗的多功能制剂。
光敏剂是光动力疗法的重要组成部分。然而，典型的光敏剂通常遇到水溶性差、非特异性肿瘤靶向、聚集猝灭（ACQ）等问题，这严重降低了 PDT 的疗效。本研究设计了一种用于癌症治疗的光动力治疗的线粒体靶向和 ROS 敏感的超分子有机骨架（SOF），可完全克服光敏剂（PSs）应用中的瓶颈。SOF 是通过结合四-β-环糊精-卟啉光敏剂和利用主体-客体超分子策略连接的 ROS 敏感硫代缩酮连接的金刚烷二聚体单元来构建的。独特的超分子骨架不仅完全解决了卟啉光敏剂的聚集猝灭问题，而且还赋予它们显著增强的水溶性。此外，通过各自的物理封装和主体-客体相互作用，SOF 可以很容易地进行功能化以纳入抗癌药物阿霉素和靶向线粒体的分子。
