The Chemo-Immunotherapeutic Roles of Tumor-Derived Extracellular Vesicle-Based Paclitaxel Delivery System in Hepatocarcinoma.

As a first-line chemotherapeutic agent, albumin-bound paclitaxel (PA) has a considerable effect on the treatment of various cancers. However, in chemotherapy for hepatocarcinoma, the sensitivity to PA is low owing to the innate resistance of hepatocarcinoma cells; the toxicity and side effects are severe, and the clinical treatment impact is poor. In this study, we present a unique nanodrug delivery system. The ultraviolet (UV)-induced tumor-cell-derived extracellular vesicles (EVs) were isolated and purified by differential centrifugation. Then, PA was loaded by coextrusion to create a vesicle drug delivery system (EVPA). By employing the EV-dependent enhanced retention effect and specific homing effect, EVPA would passively and actively target tumor tissues, activate the immune response to release PA, and achieve the combination therapeutic effect of chemo-immunotherapy on hepatocarcinoma. We demonstrated that the tumor-killing effect of EVPA is superior to that of PA, both in vivo and in vitro and that EVPA can be effectively taken up by hepatocarcinoma and dendritic cells, activate the body's specific immune response, promote the infiltration of CD4+ and CD8+ T cells in tumor tissues, and exert a precise killing effect on hepatocarcinoma cells via chemo-immunotherapy.

FBXW7 inhibits the progression of ESCC by directly inhibiting the stemness of tumor cells.

F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of gene expressions associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.

Tumor-derived extracellular vesicle drug delivery system for chemo-photothermal-immune combination cancer treatment.

Tumor extracellular vesicles (EVs) demonstrate considerable promise for medication delivery and tumor targeting owing to their natural long-term blood circulation and tissue targeting capabilities. We extracted EVs from mouse breast cancer cell 4T1 using UV stimulation and differential centrifugation. To create a new nano-drug delivery system, the vesicle delivery system (EPM) loaded with melanin and paclitaxel albumin (PA), the collected EVs were repeatedly compressed on a 200 nm porous polycarbonate membrane with melanin and PA. Our findings suggest that EPM is readily absorbed by breast cancer and dendritic cells. EPM generates significant photoacoustic signals and photothermal effects when exposed to near-infrared light and can enhance the infiltration of CD8+ T cells in mouse tumor tissues. EPM is more cytotoxic than PA in in vivo and in vitro investigations. The efficacy of EPM in clinical transformation when paired with chemotherapy/photothermal/immunotherapy treatment is demonstrated in this study.