دورية أكاديمية
أعرض في EDS

Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature.

التفاصيل البيبلوغرافية
العنوان: Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature.
المؤلفون: Khan OF; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Zaia EW; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Jhunjhunwala S; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Xue W; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ‡Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Cai W; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Yun DS; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Barnes CM; ∥Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, United States., Dahlman JE; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ⊥Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Dong Y; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; §Department of Anesthesiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, United States., Pelet JM; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Webber MJ; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Tsosie JK; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Jacks TE; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ‡Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; #Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Langer R; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ⊥Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ∇Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Anderson DG; †Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ⊥Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; ∇Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
المصدر: Nano letters [Nano Lett] 2015 May 13; Vol. 15 (5), pp. 3008-16. Date of Electronic Publication: 2015 Apr 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101088070 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6992 (Electronic) Linking ISSN: 15306984 NLM ISO Abbreviation: Nano Lett Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Chemical Society, c2001-
مواضيع طبية MeSH: Gene Transfer Techniques*, Dendrimers/*chemistry , Nanostructures/*chemistry , RNA, Small Interfering/*chemistry, Animals ; Dendrimers/therapeutic use ; Endothelial Cells/drug effects ; Humans ; Lung/drug effects ; Lung/pathology ; Nanostructures/therapeutic use ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/therapeutic use
مستخلص: Targeted RNA delivery to lung endothelial cells has the potential to treat conditions that involve inflammation, such as chronic asthma and obstructive pulmonary disease. To this end, chemically modified dendrimer nanomaterials were synthesized and optimized for targeted small interfering RNA (siRNA) delivery to lung vasculature. Using a combinatorial approach, the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length. The top performing materials from in vivo screens were found to primarily target Tie2-expressing lung endothelial cells. At high doses, the dendrimer-lipid derivatives did not cause chronic increases in proinflammatory cytokines, and animals did not suffer weight loss due to toxicity. We believe these materials have potential as agents for the pulmonary delivery of RNA therapeutics.
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معلومات مُعتمدة: U54 CA151884 United States CA NCI NIH HHS; K99 CA169512 United States CA NCI NIH HHS; R00 CA169512 United States CA NCI NIH HHS; United States Howard Hughes Medical Institute; 1K99CA169512 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: in vivo; modified dendrimer nanoparticles; nanomaterial; siRNA; target lung endothelial cells
المشرفين على المادة: 0 (Dendrimers)
0 (RNA, Small Interfering)
تواريخ الأحداث: Date Created: 20150320 Date Completed: 20160204 Latest Revision: 20200930
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4825876
DOI: 10.1021/nl5048972
PMID: 25789998
قاعدة البيانات: MEDLINE
الوصف
تدمد:1530-6992
DOI:10.1021/nl5048972