Smart nanocarriers attract considerable interest in the filed of precision nanomedicine. Dynamic control of the interaction between nanocarriers and cells offers the feasibility that in situ activates cellular internalization at the targeting sites. Herein, we demonstrate a novel class of enzyme-responsive asymmetric polymeric vesicles self-assembled from matrix metalloproteinase (MMP)-cleavable peptide-linked triblock copolymer, poly(ethylene glycol)-GPLGVRG-b-poly(ε-caprolactone)-b-poly(3-guanidinopropyl methacrylamide) (PEG-GPLGVRG-PCL-PGPMA), in which the cell-penetrating PGPMA segments asymmetrically distribute in the outer and inner shells with fractions of 9% and 91%, respectively. Upon treatment with MMP-2 to cleave the stealthy PEG shell, the vesicles undergo morphological transformation into fused multicavity vesicles and small nanoparticles, accompanied by redistribution of PGPMA segments with 76% exposed to the outside. The vesicles after dePEGylation show significantly increased cellular internalization efficiency (∼10 times) as compared to the original ones due to the triggered availability of cell-penetrating shells. The vesicles loading hydrophobic anticancer drug paclitaxel (PTX) in the membrane exhibit significantly enhanced cytotoxicity against MMP-overexpressing HT1080 cells and multicellular spheroids. The proposed vesicular system can serve as a smart nanoplatform for in situ activating intracellular drug delivery in MMP-enriched tumors.
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http://dx.doi.org/10.1021/acsami.7b02808 | DOI Listing |
J Asthma Allergy
January 2025
Amgen Inc., Thousand Oaks, CA, USA.
Airway inflammation, a hallmark feature of asthma, drives many canonical features of the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as the dominant mechanism of asthma pathogenesis, largely due to the success of inhaled corticosteroids and biologic therapies targeting components of the T2 pathway, including IL-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP). However, up to 30% of patients may lack signatures of meaningful T2 inflammation (ie, T2 low).
View Article and Find Full Text PDFMed Gas Res
June 2025
Research Department, Plovdiv Medical University, Plovdiv, Bulgaria.
Medical gases were primarily used for respiratory therapy and anesthesia, which showed promising potential in the cancer therapy. Several physiological and pathological processes were affected by the key gases, such as oxygen, carbon dioxide, nitric oxide, hydrogen sulfide, and carbon monoxide. Oxygen targets shrinking the tumor via hyperbaric oxygen therapy, and once combined with radiation therapy it enhances its effect.
View Article and Find Full Text PDFToxicology
January 2025
Department of Pharmacology, Shanghai Tenth People's Hospital Affiliated to School of Medicine of Tongji University, Shanghai, China. Electronic address:
Acetaminophen (APAP) stands as one of the most prevalent triggers of drug-induced acute liver injury (ALI). The intricate modulation of immune system activation and inflammatory cascades by hepatic immune cells is paramount in managing liver injury and subsequent restoration. In this study, we employed an integrative approach that fused our proprietary flow cytometry analyses across various time points post-APAP injury with publicly available single-cell RNA sequencing (scRNA-seq) datasets, encompassing time-series data from liver tissue of mice subjected to APAP intoxication.
View Article and Find Full Text PDFJ Allergy Clin Immunol Pract
January 2025
Pediatric Allergy Unit, Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy. Electronic address:
Background: Reintroduction of offending food in pediatric patients affected by Food Protein-Induced Enterocolitis Syndrome (FPIES) is carried out in hospitals with Oral Food Challenge (OFC), which leads to long waiting time and increases the societal burden of medical cost and human resources.
Objective: The aim of the study is to assess severity trend of acute FPIES adverse reactions over time in the same patient for possible outpatient or home reintroduction of offending food.
Methods: All children (<18 years-old) with a diagnosis of acute FPIES referred to 2 Italian pediatric allergy clinics were retrospectively enrolled.
Pharmacol Ther
January 2025
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, USA; Centers for Molecular Medicine and Genetics, Wayne State University, USA; Karmanos Cancer Institute, Detroit, MI, USA. Electronic address:
Skin wound healing is a dynamic process consisting of multiple cellular and molecular events that must be tightly coordinated to repair the injured tissue efficiently. The healing pace is decided by the type of injuries, the depth and size of the wounds, and whether wound infections occur. However, aging, comorbidities, genetic factors, hormones, and nutrition also impact healing outcomes.
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