Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma

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....

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Main Authors: Meng Wang, Chen-Yan Lv, Shu-Ang Li, Jun-Kuan Wang, Wen-Zheng Luo, Pei-Chao Zhao, Xue-You Liu, Ze-Ming Wang, Yang Jiao, Hong-Wei Sun, Yi Zhao, Peng Zhang
Format: Article
Language:English
Published: BMC 2021-07-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-021-00907-3
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author Meng Wang
Chen-Yan Lv
Shu-Ang Li
Jun-Kuan Wang
Wen-Zheng Luo
Pei-Chao Zhao
Xue-You Liu
Ze-Ming Wang
Yang Jiao
Hong-Wei Sun
Yi Zhao
Peng Zhang
author_facet Meng Wang
Chen-Yan Lv
Shu-Ang Li
Jun-Kuan Wang
Wen-Zheng Luo
Pei-Chao Zhao
Xue-You Liu
Ze-Ming Wang
Yang Jiao
Hong-Wei Sun
Yi Zhao
Peng Zhang
author_sort Meng Wang
collection DOAJ
description 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
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spelling doaj.art-75bcd64556364e19974e295ec064e0292022-12-22T04:09:59ZengBMCJournal of Nanobiotechnology1477-31552021-07-0119111810.1186/s12951-021-00907-3Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against gliomaMeng Wang0Chen-Yan Lv1Shu-Ang Li2Jun-Kuan Wang3Wen-Zheng Luo4Pei-Chao Zhao5Xue-You Liu6Ze-Ming Wang7Yang Jiao8Hong-Wei Sun9Yi Zhao10Peng Zhang11Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityThe Second Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Translational Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-021-00907-3GliomaExtracellular vesiclesNear infrared lightIndocyanine greenPaclitaxelRGE
spellingShingle Meng Wang
Chen-Yan Lv
Shu-Ang Li
Jun-Kuan Wang
Wen-Zheng Luo
Pei-Chao Zhao
Xue-You Liu
Ze-Ming Wang
Yang Jiao
Hong-Wei Sun
Yi Zhao
Peng Zhang
Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
Journal of Nanobiotechnology
Glioma
Extracellular vesicles
Near infrared light
Indocyanine green
Paclitaxel
RGE
title Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
title_full Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
title_fullStr Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
title_full_unstemmed Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
title_short Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
title_sort near infrared light fluorescence imaging guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma
topic Glioma
Extracellular vesicles
Near infrared light
Indocyanine green
Paclitaxel
RGE
url https://doi.org/10.1186/s12951-021-00907-3
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