دورية أكاديمية
أعرض في EDS

Bottlebrush Polyethylene Glycol Nanocarriers Translocate across Human Airway Epithelium via Molecular Architecture-Enhanced Endocytosis.

التفاصيل البيبلوغرافية
العنوان: Bottlebrush Polyethylene Glycol Nanocarriers Translocate across Human Airway Epithelium via Molecular Architecture-Enhanced Endocytosis.
المؤلفون: He ZJ; Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22904, United States., Huang B; Soft Biomatter Laboratory, Department of Materials Science and Engineering, University of Virginia, Charlottesville, Virginia 22904, United States., Cai LH; Soft Biomatter Laboratory, Department of Materials Science and Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.; Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.; Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
المصدر: ACS nano [ACS Nano] 2024 Jul 09; Vol. 18 (27), pp. 17586-17599. Date of Electronic Publication: 2024 Jun 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101313589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1936-086X (Electronic) Linking ISSN: 19360851 NLM ISO Abbreviation: ACS Nano Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington D.C. : American Chemical Society
مواضيع طبية MeSH: Polyethylene Glycols*/chemistry , Endocytosis* , Drug Carriers*/chemistry, Humans ; Nanoparticles/chemistry ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/cytology ; Particle Size ; Drug Delivery Systems ; Cell Proliferation/drug effects
مستخلص: Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, the human airway surface presents multiple barriers to efficient drug delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by a molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1000) low molecular weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture-enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a carrier for pulmonary and mucosal drug delivery.
التعليقات: Update of: bioRxiv. 2024 Feb 16:2024.02.15.580508. doi: 10.1101/2024.02.15.580508. (PMID: 38405944)
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معلومات مُعتمدة: P30 DK065988 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: bottlebrush; drug delivery; endocytosis; human airway; mucus; polyethylene glycol
المشرفين على المادة: 3WJQ0SDW1A (Polyethylene Glycols)
0 (Drug Carriers)
تواريخ الأحداث: Date Created: 20240627 Date Completed: 20240709 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC11238595
DOI: 10.1021/acsnano.4c01983
PMID: 38932624
قاعدة البيانات: MEDLINE
الوصف
تدمد:1936-086X
DOI:10.1021/acsnano.4c01983