Author:
Wang Meng,Lv Chen-Yan,Li Shu-Ang,Wang Jun-Kuan,Luo Wen-Zheng,Zhao Pei-Chao,Liu Xue-You,Wang Ze-Ming,Jiao Yang,Sun Hong-Wei,Zhao Yi,Zhang Peng
Abstract
Abstract
Background
We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma.
Methods
Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo.
Results
Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group.
Conclusion
ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.
Graphic Abstract
Funder
Medical Science and Technology Project of Henan Province
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Reference35 articles.
1. Cheng M, Zhang ZW, Ji XH, Xu Y, Bian E, Zhao B. Super-enhancers: a new frontier for glioma treatment. Biochim Biophys Acta Rev Cancer. 2020;1873:188353.
2. Chen W, Lei C, Liu P, et al. Progress and prospects of recurrent glioma: a recent scientometric analysis of the web of science in 2019. World Neurosurg. 2020;134:e387–99.
3. Taal W, Bromberg JE, van den Bent MJ. Chemotherapy in glioma. CNS. Oncol. 2015;4:179–92.
4. Ziu M, Kalkanis SN, Gilbert M, Ryken TC, Olson JJ. The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2015;125:585–607.
5. Lee Titsworth W, Murad GJ, Hoh BL, Rahman M. Fighting fire with fire: the revival of thermotherapy for gliomas. Anticancer Res. 2014;34:565–74.
Cited by
20 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献