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AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. Therefore, we intend to explore novel strategies against PDAC. The exosomes-based biomimetic nanoparticle is an appealing candidate served as a drug carrier in cancer treatment, due to its inherit abilities. In the present study, we designed dasatinib-loaded hybrid exosomes by fusing human pancreatic cancer cells derived exosomes with dasatinib-loaded liposomes, followed by characterization for particle size (119.9 ± 6.10 nm) and zeta potential (−11.45 ± 2.24 mV). Major protein analysis from western blot techniques reveal the presence of exosome marker proteins CD9 and CD81. PEGylated hybrid exosomes showed pH-sensitive drug release in acidic condition, benefiting drug delivery to acidic cancer environment. Dasatinib-loaded hybrid exosomes exhibited significantly higher uptake rates and cytotoxicity to parent PDAC cells by two-sample t-test or by one-way ANOVA analysis of variance, as compared to free drug or liposomal formulations. The results from our computational analysis demonstrated that the drug-likeness, ADMET, and protein-ligand binding affinity of dasatinib are verified successfully. Cancer derived hybrid exosomes may serve as a potential therapeutic candidate for pancreatic cancer treatment.

BackgroundArtificial intelligence-assisted gastroscopy (AIAG) based on deep learning has been validated in various scenarios, but there is a lack of studies regarding diagnosing neoplasms under white light endoscopy. This study explored the potential role of AIAG systems in enhancing the ability of endoscopists to diagnose gastric tumor lesions under white light.MethodsA total of 251 patients with complete pathological information regarding electronic gastroscopy, biopsy, or ESD surgery in Xi’an Gaoxin Hospital were retrospectively collected and comprised 64 patients with neoplasm lesions (excluding advanced cancer) and 187 patients with non-neoplasm lesions. The diagnosis competence of endoscopists with intermediate experience and experts was compared for gastric neoplasms with or without the assistance of AIAG, which was developed based on ResNet-50.ResultsFor the 251 patients with difficult clinical diagnoses included in the study, compared with endoscopists with intermediate experience, AIAG’s diagnostic competence was much higher, with a sensitivity of 79.69% (79.69% vs. 72.50%, p = 0.012) and a specificity of 73.26% (73.26% vs. 52.62%, p

Chemoresistance is a main limitation for the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, the authors show that an antibody drug conjugate-like compound targeting both EGFR and HER2 overcomes gemcitabine resistance in PDAC preclinical models by mechanisms involving the tumour suppressor SMAD4.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a refractory malignant tumor with poor prognosis, limited chemotherapeutic efficacy, and only about 5% of 5‐year survival rate. We generated a dual‐targeting ligand‐based lidamycin (DTLL) to investigate its efficacy against pancreatic cancer after preparing its precursor, DTLP. DTLP was shown specifically binding to EGFR and HER2 on cell surface, followed by endocytosis into cytoplasm of pancreatic cancer cells. DTLL significantly promoted apoptosis and cell cycle arrest at G2/M stages and inhibited cell proliferation. Pancreatic tumors of either MIA‐paca‐2 cell line‐derived (CDX) or patient‐derived xenograft (PDX) mouse models were significantly regressed in response to DTLL. It suggested that DTLL might be a highly potent bispecific antibody‐drug conjugate (ADC)‐like agent for pancreatic cancer therapy. LDM is known to function as an antitumor cytotoxic agent by its induction of DNA damage in cancer cells, therefore, DTLL, as its derivative, also showed similar cytotoxicity. However, we found that DTLL might reverse the AKT/mTOR feedback activation induced by LDM at the first time. The results from both in vitro and in vivo experiments suggested that DTLL enhanced DNA damage via EGFR/HER2‐dependent blockage of PI3K/AKT/mTOR and PD‐L1 signaling pathways in cancer cells, leading to the inhibition of cell proliferation and immunosurveillance escape from pancreatic tumor. Our studies on DTLL functional characterization revealed its novel mechanisms on internal enhancement of DNA damage and implied that DTLL might provide a promising targeted therapeutic strategy for pancreatic cancer.

The potentials of activated carbon nanoparticles (ACNP) as anticancer drug carriers were studied. ACNP were prepared with a top-down method. ACNP-based drug delivery system of docetaxel (ACNP-DOC) was prepared with a simple absorption method and its effects were studied primarily with methyl thiazolyl tetrazolium (MTT) assay, light microscope (LM), atomic force microscope (AFM) and transmission electron microscope (TEM). The prepared ACNP were approximately globular in shape with an average size of 233 nm, which had a saturate adsorption of 195.69 mg/g at mass ratio of ACNP: DOC=5:1. The drug delivery system prepared by adsorbing of ACNP for DOC had excellent releasing profile in the simulated in vivo environment. LM observation showed that ACNP can accumulate around the cells and on the surface of cells and TEM revealed that ACNP can enter cells and nuclears. MTT test demonstrated that ACNP-DOC had inhibitive effects on the growth of A549 cells, with an IC50 of 0.79 μg/ml, significantly smaller than that of 20 μg/ml of free DOC, indicating ACNP-DOC had stronger effects than free DOC. The imaging of AFM showed that both DOC and ACNP-DOC caused significant pathological changes of the cell membrane, including rough surfaces, large grains and holes, but these pathological changes were more obvious in ACNP-DOC treated cells than those free DOC treated ones. In all of the experiments, ACNP themselves had no significant influences on A549 cells. It was concluded that ACNP could serve as a good nanocarrier for anti-cancer drug delivery to target cells and have a great potential application in antitumor chemotherapy.