Design of 18 nm Doxorubicin-Loaded 3-Helix Micelles: Cellular Uptake and Cytotoxicity in Patient-Derived GBM6 Cells.

التفاصيل البيبلوغرافية
العنوان:	Design of 18 nm Doxorubicin-Loaded 3-Helix Micelles: Cellular Uptake and Cytotoxicity in Patient-Derived GBM6 Cells.
المؤلفون:	Jung BT; Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, California 94720, United States., Jung K; Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States., Lim M; UCB-UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California 94720, United States., Li M; Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States., Santos R; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94158, United States., Ozawa T; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94158, United States., Xu T; Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, California 94720, United States.; Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.; Material Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
المصدر:	ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2021 Jan 11; Vol. 7 (1), pp. 196-206. Date of Electronic Publication: 2020 Dec 18.
نوع المنشور:	Journal Article; 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: 101654670 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-9878 (Electronic) Linking ISSN: 23739878 NLM ISO Abbreviation: ACS Biomater Sci Eng Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, DC : American Chemical Society, [2015]-
مواضيع طبية MeSH:	Antineoplastic Agents* , Micelles*, Biological Transport ; Doxorubicin ; Humans ; Tissue Distribution
مستخلص:	The fate of nanocarrier materials at the cellular level constitutes a critical checkpoint in the development of effective nanomedicines, determining whether tissue level accumulation results in therapeutic benefit. The cytotoxicity and cell internalization of ∼18 nm 3-helix micelle (3HM) loaded with doxorubicin (DOX) were analyzed in patient-derived glioblastoma (GBM) cells in vitro . The half-maximal inhibitory concentration (IC 50 ) of 3HM-DOX increased to 6.2 μg/mL from <0.5 μg/mL for free DOX in patient-derived GBM6 cells, to 15.0 μg/mL from 6.5 μg/mL in U87MG cells, and to 21.5 μg/mL from ∼0.5 μg/mL in LN229 cells. Modeling analysis of previous 3HM biodistribution results predicts that these cytotoxic concentrations are achievable with intravenous injection in rodent GBM models. 3HM-DOX formulations were internalized intact and underwent intracellular trafficking distinct from free DOX. 3HM was quantified to have an internalization half-life of 12.6 h in GBM6 cells, significantly longer than that reported for some liposome and polymer systems. 3HM was found to traffic through active endocytic processes, with clathrin-mediated endocytosis being the most involved of the pathways studied. Inhibition studies suggest substantial involvement of receptor recognition in 3HM uptake. As the 3HM surface is PEG-ylated with no targeting functionalities, protein corona-cell surface interactions, such as the apolipoprotein-low-density lipoprotein receptor, are expected to initiate internalization. The present work gives insights into the cytotoxicity, pharmacodynamics, and cellular interactions of 3HM and 3HM-DOX relevant for ongoing preclinical studies. This work also contributes to efforts to develop predictive mathematical models tracking the accumulation and biodistribution kinetics at a systemic level.
فهرسة مساهمة:	Keywords: PEGylation; cellular uptake; glioblastoma; nano−bio interface; patient-derived xenograft; peptide amphiphiles
المشرفين على المادة:	0 (Antineoplastic Agents) 0 (Micelles) 80168379AG (Doxorubicin)
تواريخ الأحداث:	Date Created: 20201218 Date Completed: 20210514 Latest Revision: 20210514
رمز التحديث:	20231215
DOI:	10.1021/acsbiomaterials.0c01639
PMID:	33338381
قاعدة البيانات:	MEDLINE

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الوصف
تدمد:	2373-9878
DOI:	10.1021/acsbiomaterials.0c01639