دورية أكاديمية
Computationally guided high-throughput design of self-assembling drug nanoparticles.
| العنوان: | Computationally guided high-throughput design of self-assembling drug nanoparticles. |
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| المؤلفون: | Reker D; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Rybakova Y; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Kirtane AR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Cao R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Division of Engineering Science, University of Toronto, Toronto, Ontario, Canada., Yang JW; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA., Navamajiti N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Biomedical Engineering Program, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand., Gardner A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Zhang RM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Esfandiary T; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., L'Heureux J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., von Erlach T; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Smekalova EM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Leboeuf D; Skolkovo Institute of Science and Technology, Moscow, Russia., Hess K; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Lopes A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Rogner J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Collins J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Tamang SM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Ishida K; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Chamberlain P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Yun D; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Lytton-Jean A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Soule CK; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Cheah JH; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Hayward AM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Langer R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Traverso G; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. cgt20@mit.edu.; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. cgt20@mit.edu. |
| المصدر: | Nature nanotechnology [Nat Nanotechnol] 2021 Jun; Vol. 16 (6), pp. 725-733. Date of Electronic Publication: 2021 Mar 25. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101283273 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-3395 (Electronic) Linking ISSN: 17483387 NLM ISO Abbreviation: Nat Nanotechnol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group, 2006- |
| مواضيع طبية MeSH: | Drug Carriers/*chemistry , High-Throughput Screening Assays/*methods , Nanoparticles/*chemistry , Sorafenib/*pharmacology , Terbinafine/*pharmacology, Animals ; Candida albicans/drug effects ; Computer Simulation ; Drug Carriers/chemical synthesis ; Drug Design ; Drug Evaluation, Preclinical/methods ; Dynamic Light Scattering ; Excipients/chemistry ; Female ; Glycyrrhizic Acid/chemistry ; Humans ; Machine Learning ; Mice, Inbred Strains ; Skin Absorption ; Sorafenib/chemistry ; Sorafenib/pharmacokinetics ; Taurocholic Acid/chemistry ; Terbinafine/chemistry ; Tissue Distribution ; Xenograft Model Antitumor Assays ; Mice |
| مستخلص: | Nanoformulations of therapeutic drugs are transforming our ability to effectively deliver and treat a myriad of conditions. Often, however, they are complex to produce and exhibit low drug loading, except for nanoparticles formed via co-assembly of drugs and small molecular dyes, which display drug-loading capacities of up to 95%. There is currently no understanding of which of the millions of small-molecule combinations can result in the formation of these nanoparticles. Here we report the integration of machine learning with high-throughput experimentation to enable the rapid and large-scale identification of such nanoformulations. We identified 100 self-assembling drug nanoparticles from 2.1 million pairings, each including one of 788 candidate drugs and one of 2,686 approved excipients. We further characterized two nanoparticles, sorafenib-glycyrrhizin and terbinafine-taurocholic acid both ex vivo and in vivo. We anticipate that our platform can accelerate the development of safer and more efficacious nanoformulations with high drug-loading capacities for a wide range of therapeutics. |
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| معلومات مُعتمدة: | 168827 Switzerland SNSF_ Swiss National Science Foundation; P30 CA014051 United States CA NCI NIH HHS; R01 EB000244 United States EB NIBIB NIH HHS; R37 EB000244 United States EB NIBIB NIH HHS |
| المشرفين على المادة: | 0 (Drug Carriers) 0 (Excipients) 5E090O0G3Z (Taurocholic Acid) 6FO62043WK (Glycyrrhizic Acid) 9ZOQ3TZI87 (Sorafenib) G7RIW8S0XP (Terbinafine) |
| تواريخ الأحداث: | Date Created: 20210326 Date Completed: 20210906 Latest Revision: 20240923 |
| رمز التحديث: | 20240923 |
| مُعرف محوري في PubMed: | PMC8197729 |
| DOI: | 10.1038/s41565-021-00870-y |
| PMID: | 33767382 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1748-3395 |
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| DOI: | 10.1038/s41565-021-00870-y |