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EGFR-targeting RNase A-cetuximab antibody-drug conjugate induces ROS-mediated apoptosis to overcome drug resistance in KRAS mutant cancer cells.
Sci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFProtein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.
Theranostics
January 2025
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The tumor microenvironment (TME) is involved in cancer initiation and progression. With advances in the TME field, numerous therapeutic approaches, such as antiangiogenic treatment and immune checkpoint inhibitors, have been inspired and developed. Nevertheless, the sophisticated regulatory effects on the biological balance of the TME remain unclear.
View Article and Find Full Text PDFDetectEV: A functional enzymatic assay to assess integrity and bioactivity of extracellular vesicles.
J Extracell Vesicles
January 2025
Cell-Tech HUB and Institute for Research and Biomedical Innovation (IRIB), National Research Council of Italy (CNR), Palermo, Italy.
The application of extracellular vesicles (EVs) as therapeutics or nanocarriers in cell-free therapies necessitates meticulous evaluations of different features, including their identity, bioactivity, batch-to-batch reproducibility, and stability. Given the inherent heterogeneity in EV preparations, this assessment demands sensitive functional assays to provide key quality control metrics, complementing established methods to ensure that EV preparations meet the required functionality and quality standards. Here, we introduce the detectEV assay, an enzymatic-based approach for assessing EV luminal cargo bioactivity and membrane integrity.
View Article and Find Full Text PDFIdentifying representative sequences of protein families using submodular optimization.
Sci Rep
January 2025
Department of Computer Science and Software Engineering, Auburn University, Auburn, AL, 36849, USA.
Identifying representative sequences for groups of functionally similar proteins and enzymes poses significant computational challenges. In this study, we applied submodular optimization, a method effective in data summarization, to select representative sequences for thioesterase enzyme families. We introduced and validated two algorithms, Greedy and Bidirectional Greedy, using curated protein sequence data from the ThYme (Thioester-active enzYmes) database.
View Article and Find Full Text PDFStructure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry, Duke University, Durham, NC 27708.
Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.
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