Although induction of ferroptosis and inhibition of transforming growth factor-β (TGF-β) signaling are both effective ways to reform the tumor microenvironment (TME) and render low-immunogenic tumors responsive to immune checkpoint inhibitor therapy, dose-limiting side effects remain major obstacles hindering their clinical application. Herein, novel sorafenib and anti-TGF-β antibody loaded Fe O /Gd O hybrid nanoparticles with conjugation of arginine-glycine-aspartic dimer (FeGd-HN@Sorafenib@TGF-β-antibody@RGD2, FG-STR) are developed. Sorafenib significantly enhances FeGd-HN-triggered ferroptosis and improves maturation and phagocytosis of dendritic cells (DCs) by inducing damage-associated molecular patterns released from ferroptotic cancer cells, while the anti-TGF-β antibody further synergizes with enhanced ferroptosis to promote DC maturation and the recruitment of CD8 T cells, thus heating the TME. Moreover, the incorporation of RGD2 facilitates the uptake of the FG-STR in tumor cells which lead to a significant dosage reduction of both sorafenib and anti-TGF-β antibody to avoid dose-limiting toxicities. Finally, in vitro and in vivo experiments show that FG-STR has significantly superior intrinsic magnetic resonance imaging (MRI) capability than that of Gadovist, effectively inhibits tumor growth and lung metastasis, and increases the efficacy of anti-programmed cell death-1 treatment. Taken together, this study provides a promising strategy for new advanced MRI-guided TME heating therapies.
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http://dx.doi.org/10.1002/adhm.202300176 | DOI Listing |
J Nanobiotechnology
January 2025
Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor "lymphocyte function-associated antigen-1" (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18).
View Article and Find Full Text PDFHum Genomics
January 2025
Department of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, 00133, Rome, Italy.
Background: The Immunoglobulin Heavy Chain (IGH) genomic region is responsible for the production of circulating antibodies and warrants careful investigation for its association with COVID-19 characteristics. Multiple allelic variants within and across different IGH gene segments form a limited set of haplotypes. Previous studies have shown associations between some of these haplotypes and clinical outcomes of COVID-19.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Background: HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete response remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for the management of dyslipidemia by enhancing the clearance of low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 and cancer cells.
View Article and Find Full Text PDFItal J Pediatr
January 2025
Department of Pediatrics, IRCCS Policlinico San Matteo Foundation, Viale Golgi 19, Pavia, 27100, Italy.
Background: Chronic Nonbacterial Osteomyelitis (CNO) is a rare auto-inflammatory disease that mainly affects children, and manifests with single or multiple painful bone lesions. Due to the lack of specific laboratory markers, CNO diagnosis is a matter of exclusion from different conditions, first and foremost bacterial osteomyelitis and malignancies. Whole Body Magnetic Resonance (WBMR) and bone biopsy are the gold standard for the diagnosis.
View Article and Find Full Text PDFFluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
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