دورية أكاديمية
Mathematical Modeling and Experimental Validation of Extracellular Vesicle-Mediated Tumor Suppressor MicroRNA Delivery and Propagation in Ovarian Cancer Cells.
| العنوان: | Mathematical Modeling and Experimental Validation of Extracellular Vesicle-Mediated Tumor Suppressor MicroRNA Delivery and Propagation in Ovarian Cancer Cells. |
|---|---|
| المؤلفون: | Gandham SK; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States., Attarwala HZ; Moderna Therapeutics, Inc., Cambridge, Massachusetts 02139, United State., Amiji MM; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.; Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, Massachusetts 02115, United State. |
| المصدر: | Molecular pharmaceutics [Mol Pharm] 2022 Nov 07; Vol. 19 (11), pp. 4067-4079. Date of Electronic Publication: 2022 Oct 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2004- |
| مواضيع طبية MeSH: | MicroRNAs*/genetics , MicroRNAs*/metabolism , Extracellular Vesicles*/metabolism , Ovarian Neoplasms*/metabolism, Humans ; Female ; Vascular Endothelial Growth Factor A/metabolism ; Models, Theoretical ; Tumor Microenvironment |
| مستخلص: | Extracellular vesicle (EV)-mediated microRNA transfer and propagation from the donor cell to the recipient cell in the tumor microenvironment have significant implications, including the development of multidrug resistance (MDR). Although miRNA-encapsulated EV have been shown to have functional effects on recipient cells, the quantitative aspects of transfer kinetics and functional effects remain poorly understood. Intracellular events such as degradation of miRNA, loading of miRNA into EVs, cellular release of EVs, and their uptake by recipient cells govern the transfer and functional effect of encapsulated miRNA. Based on these rate-limiting steps, we developed a mathematical model using ordinary differential equations (model 1). We performed coculture experiments using ID8-VEGF ovarian cancer cells to demonstrate EV-mediated propagation of tumor suppressor miRNA Let7b administered with hyaluronic acid-poly(ethyleneimine) (HA-PEI) nanoparticles. Using the experimental data and model fitting, we determined the rate constants for the kinetic events involved in the transfer from the donor cells to the recipient cells. In model 2, we performed Let7b transfection experiments in ID8-VEGF cells with HA-PEI nanoparticles to determine the concentration-effect relationship on HMGA2 mRNA levels. Lastly, in model 3, we combined model 1 and model 2 parameters to describe the kinetics and effect relationship of EV-Let7b in recipient cells to predict the minimum number of miRNA copies needed to show functional effects. |
| معلومات مُعتمدة: | R21 CA179652 United States CA NCI NIH HHS; R56 CA198492 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Let7b; extracellular vesicles; mathematical modeling; microRNA; ovarian cancer |
| المشرفين على المادة: | 0 (MicroRNAs) 0 (Vascular Endothelial Growth Factor A) |
| تواريخ الأحداث: | Date Created: 20221013 Date Completed: 20221108 Latest Revision: 20221205 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1021/acs.molpharmaceut.2c00525 |
| PMID: | 36226722 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1543-8392 |
|---|---|
| DOI: | 10.1021/acs.molpharmaceut.2c00525 |