Aloe vera-derived extracellular vesicle-like particles suppress pancreatic carcinoma progression through triggering...

Pancreatic carcinoma (PC) remains one of the most aggressive malignancies that is often referred to as the "king of cancers" in clinic. Plant-derived extracellular vesicle-like particles (p-EVLP) has demonstrated broad-spectrum antitumor potential through their unique ability to effectively penetrate tumor microenvironments and deliver bioactive compounds. Aloe Vera is a tender and juicy plant with anti-tumor properties, while whether Aloe Vera-derived EVLP (AV-EVLP) can inhibit PC and what the underlying mechanism is still unclear.

Two kinds of AV-EVLPs (EV-U and EV-P) were isolated from Aloe vera using comparative purification techniques. Their structure and composition characterization were performed using TEM, NTA and UHPLC-QTOFMS. In vitro experiments using Panc-1 cells included cytotoxicity, migration/invasion and cellular uptake assay were employed to investigate their tumor inhibition potential. In a Panc-1 xenograft mouse model, the therapeutic effects and systemic toxicity of EV-U were evaluated through tumor volume and weight, Ki67, TUNEL and histopathology examination. Mechanistic studies involved the levels of cellular ROS, IL-1β, IL-18 and the expression of caspase-1/3/7/9-GSDMD/E in both cell and tumor tissues were determined by ELISA, immunohistochemistry, Western blot and qRT-PCR.

EV-U and EV-P exhibited characteristic cup-shaped morphology with mean diameters 179.3 nm and 227.1 nm, respectively. At their respective IC₅₀ concentrations, both effectively inhibit cell migration and invasion and increase ROS, LDH, IL-18, and IL-1β levels in Panc-1 cells. Comparably, EV-U exhibited better activity due to their fewer impurities and more uniform dispersion. Further in vivo experiments supported the effectiveness of EV-U in reducing tumor volume and weight without causing toxicity or immunogenicity. Mechanistically, the activation of pyroptosis through the caspase-1/3/7/9-GSDMD/E pathways contributed to its efficacy.

AV-EVLP significantly inhibit pancreatic cancer progression by triggering mitochondrial ROS release through the activation of caspase-1/3/7/9-GSDMD/E-mediated pyroptosis.