Abstract
BackgroundWe investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma.MethodsRaw264.7 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.ResultsUnder 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.ConclusionICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.Graphic
Highlights
Glioma, the most frequently occurring primary malignant malignancy in the human brain, remains as an incurable disorder despite currently available treatment protocols, including surgery, radiation, and chemotherapy [1]
indocyanine green (ICG)/PTX@Neuropilin‐1 targeting peptide (RGE)‐extracellular vesicles (EVs) were successfully established To reduce effect on immune system, nude mouse Raw264.7 cells were used as parental cells, from which EVs were isolated through ultracentrifugation
J fluorescein isothiocyanate (FITC)-positive cells identified by flow cytometry (i, U251 cells incubated with ICG/PTX@Neuropilin-1 targeting peptide (RGE)-EV; ii, U251 cells incubated with ICG/PTX@ EV and RGE; iii, U251 cells incubated with ICG/PTX@EV; iv, free U251 cells; v, FITC-labeled U251 cells)
Summary
The most frequently occurring primary malignant malignancy in the human brain, remains as an incurable disorder despite currently available treatment protocols, including surgery, radiation, and chemotherapy [1]. Of note, increasing attention has been drawn in recent years to targeted therapy and combination therapy against glioma, yet there are few available reports regarding randomized controlled trials, literature reviews, basic medical research, and meta-analyses [2]. Hyperthermia, defined as a treatment protocol induced by abnormal fever, depends on temperature and exposure while precise targeting, accurate delivery and effective doses are required [6, 7]. We sought to investigate the therapeutic effect of chemotherapy combined with hyperthermia in managing glioma. We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
