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. 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

Diagnostic Role of Extracellular Vesicles in Cancer: A Comprehensive Systematic Review and Meta-Analysis

“…Fundamentally, the metaanalysis results were based on unadjusted estimates because some studies did not provide detailed information to calculate the adjusted estimates. Definitely, chemotherapy and other therapeutic interventions can also alter the EV profile (Ab Razak et al, 2019;Wang et al, 2021), which has been out of control in reported studies. In this regard, further research should validate the diagnostic value of EV indices in cancer patients who receive different treatments, such as chemotherapy, immunotherapy, or radiotherapy, and differentiate between those treated with chemo radiation and those treated with monotherapy.…”

Recent advances in drug delivery systems for targeting brain tumors

“…ICG/PTX@RGE-EV shows good photothermal properties and promotion of PTX release from EVs, when stimulated by 808-nm laser light. Then, they target U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis, which increases the median survival of glioma mice (Wang et al., 2021 ). What’s more, the significantly reduced tumor volume was observed in mice following targeting combined therapy (ICG/PTX@RGE-EV + NIR) compared with mice treated with chemotherapy, (PTX@RGE-EV), hyperthermia (ICG@RGEEV + NIR), or non-targeted chemotherapy-hyperthermia (ICG/PTX@EV + NIR).…”

Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment

“…ICG/PTX@RGE-EV shows good photothermal properties and drug release ability. Furthermore, this DDS can target U251 cells completely, activate the Caspase-3 pathway through chemotherapy and hyperthermia, and enhance U251 cell apoptosis 161 ( Figure 5 C ).…”

“…C) ICG/PTX@RGE-EV can effectively target glioma to enact the Caspase-3 pathway through chemotherapy-hyperthermia in commitment to glioma cell apoptosis, which implies cancer development is smothered. Adapted with permission from 161 . Copyright Year 2021, Springer Nature.…”