Tumor‐Exocytosed Exosome/Aggregation‐Induced Emission Luminogen Hybrid Nanovesicles Facilitate Efficient Tumor Penetration and Photodynamic Therapy

• Published in: Angewandte Chemie International Edition 2020-08, Vol.59 (33), p.13836-13843
• Main Authors: Zhu, Daoming, Duo, Yanhong, Suo, Meng, Zhao, Yonghua, Xia, Ligang, Zheng, Zheng, Li, Yang, Tang, Ben Zhong
• Format: Article
• Language: English
• Subjects: Agglomeration; Animals; Cell Line, Tumor; Dexamethasone; Electroporation; Emission; Exocytosis; exosome/AIEgen hybrid nanovesicles; Exosomes; Exosomes - metabolism; Humans; Hybridization; Hypoxia; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Nanostructures; Normalizing; Penetration; Photochemotherapy; Photodynamic therapy; Photosensitization; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - therapeutic use; Steroids; Tissue Distribution; tumor penetration; tumor vascular normalization; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202003672

The development of novel photosensitizing agents with aggregation‐induced emission (AIE) properties has fueled significant advances in the field of photodynamic therapy (PDT). An electroporation method was used to prepare tumor‐exocytosed exosome/AIE luminogen (AIEgen) hybrid nanovesicles (DES) that could facilitate efficient tumor penetration. Dexamethasone was then used to normalize vascular function within the tumor microenvironment (TME) to reduce local hypoxia, thereby significantly enhancing the PDT efficacy of DES nanovesicles, and allowing them to effectively inhibit tumor growth. The hybridization of AIEgen and biological tumor‐exocytosed exosomes was achieved for the first time, and combined with PDT approaches by normalizing the intratumoral vasculature as a means of reducing local tissue hypoxia. This work highlights a new approach to the design of AIEgen‐based PDT systems and underscores the potential clinical value of AIEgens. Hybrid AIEgen and biological tumor‐exocytosed exosome nanovesicles (DES) were combined with photodynamic therapy (PDT) in tumor vessel normalization therapy. DES enhance tumor tissue penetration of AIEgens significantly. Dexamethasone (DEX) was used to normalize vascular function within the tumor microenvironment, thereby reducing local hypoxia and enhancing the PDT effect of DES. Key: aggregation‐induced emission luminogens (AIEgens), photosensitizer (DCPy).