Tang Yufu, Lu Xiaomei, Yin Chao, Zhao Hui, Hu Wenbo, Hu Xiaoming, Li Yuanyuan, Yang Zhen, Lu Feng, Fan Quli, Huang Wei
Key Laboratory for Organic Electronics and Information Displays , Jiangsu Key Laboratory for Biosensors , Institute of Advanced Materials (IAM) , Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) , Nanjing University of Posts & Telecommunications (NUPT) , Nanjing 210023 , China . Email:
Key Laboratory of Flexible Electronics (KLOFE) , Institute of Advanced Materials (IAM) , Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) , Nanjing Tech University (Nanjing Tech) , Nanjing 211816 , China.
Chem Sci. 2018 Nov 10;10(5):1401-1409. doi: 10.1039/c8sc04012e. eCollection 2019 Feb 7.
Tissue-penetration-depth-independent self-luminescence is highly expected to perform photoisomerization-related bioapplications to overcome the limitation of shallow tissue-penetration from external photoexcitation. However, it remains extremely challenging because of lacking a target-specific high-intensity self-luminescence to precisely and effectively drive the photoisomerization. Here, we first report a target-specific tissue-depth-independent photoisomerization by developing a target-specific initiated and -enhanced chemiluminescence (one of self-luminescence) strategy that overcomes the limitation of lacking target-specific high-intensity self-luminescence. Considering that photoisomerization shows boundless glamour in drug-controlled release for disease-specific chemotherapy, we demonstrated applicability of our strategy to apply it in tumor-specific self-luminescence-controlled drug chemotherapy. Specifically, a chemiluminescence substrate and chemiluminescence fluorophore (antitumor drug, CPT) were co-encapsulated in host-guest carriers composed of cyclodextrin and the photoisomerization molecule azobenzene. Tumor-specific HO-induced chemiluminescence preliminarily isomerizes azobenzene, triggering the partial dissociation of host-guest carriers and CPT release. Particularly, the initially released CPT again functions as a chemiluminescence enhancer to achieve enhanced chemiluminescence, assuring target-specific enhanced isomerization and CPT release. With high tumor-inhibition-rate (73%) and no obvious therapy-side-effect indicates the good efficiency and target-specificity of our chemiluminescence-driven photoisomerization. Although we only demonstrated one example of a photoisomerization-related bioapplication, namely photoisomerization-controlled drug chemotherapy, our work provides guidelines to design various target-specific tissue-depth-independent photoisomerization for bioapplications.
与组织穿透深度无关的自发光有望实现与光异构化相关的生物应用，以克服外部光激发组织穿透浅的局限性。然而，由于缺乏能够精确有效地驱动光异构化的靶向特异性高强度自发光，这仍然极具挑战性。在此，我们首次报道了一种靶向特异性的、与组织深度无关的光异构化，通过开发一种靶向特异性引发和增强的化学发光（自发光之一）策略，克服了缺乏靶向特异性高强度自发光的局限性。考虑到光异构化在疾病特异性化疗的药物控释中展现出无限魅力，我们证明了我们的策略在肿瘤特异性自发光控制药物化疗中的适用性。具体而言，将化学发光底物和化学发光荧光团（抗肿瘤药物，CPT）共包封在由环糊精和光异构化分子偶氮苯组成的主客体载体中。肿瘤特异性HO诱导的化学发光使偶氮苯初步异构化，触发主客体载体的部分解离和CPT释放。特别地，最初释放的CPT再次作为化学发光增强剂，实现增强的化学发光，确保靶向特异性增强的异构化和CPT释放。高肿瘤抑制率（73%）且无明显治疗副作用表明我们的化学发光驱动光异构化具有良好的效率和靶向特异性。尽管我们仅展示了一个与光异构化相关的生物应用实例，即光异构化控制药物化疗，但我们的工作为设计各种用于生物应用的靶向特异性、与组织深度无关的光异构化提供了指导。
