Meng Wang1, Chen-Yan Lv2, Shu-Ang Li3, Jun-Kuan Wang1, Wen-Zheng Luo1, Pei-Chao Zhao1, Xue-You Liu1, Ze-Ming Wang1, Yang Jiao1, Hong-Wei Sun4, Yi Zhao5, Peng Zhang6. 1. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China. 2. The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, People's Republic of China. 3. Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China. 4. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China. sunhongweizzu123@126.com. 5. Department of Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China. zhaoyi0910@163.com. 6. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China. 13673665325@126.com.
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.
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 gliomamice 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.
Authors: Susannah Hallal; Saeideh Ebrahimkhani; Brindha Shivalingam; Manuel B Graeber; Kimberley L Kaufman; Michael E Buckland Journal: Brain Tumor Pathol Date: 2019-03-11 Impact factor: 3.298