| 项目编号: | 1510015
|
| 项目名称: | UNS: Collaborative Research: Unique binding geometries: Engineering & Modeling of Sticky Patches on Lipid Nanoparticles for Effective Targeting of Otherwise Untargetable cells |
| 作者: | Stavroula Sofou
|
| 承担单位: | Rutgers University New Brunswick
|
| 批准年: | 2014
|
| 开始日期: | 2015-08-01
|
| 结束日期: | 2018-07-31
|
| 资助金额: | USD344185
|
| 资助来源: | US-NSF
|
| 项目类别: | Standard Grant
|
| 国家: | US
|
| 语种: | 英语
|
| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
|
| 英文关键词: | cancer cell
; sticky lipid nanoparticle
; research
; drug-carrying nanoparticle
; nanoparticle-receptor
; nanoparticle
; sticky patch
; biomedical engineering program
; nanoparticle-associated receptor
; drug-carrying
; tumor cell
; cellular internalization
; new binding geometry
; investigator
; binding time
; cell-associated nanoparticle
; multiscale modeling
; drug-carrying lipid nanoparticle
; novel binding geometry
; binding kinetics
; binding ligand
; mathematical modeling
; new geometry
; heterogeneous lipid membrane
; effective cell binding
|
| 英文摘要: | PI: Sofou, Stavroula / Kevrekidis, Yannis G.
Proposal Number: 1510015 / 1510149
This proposal aims to explore and understand the behavior of drug-carrying nanoparticles whose surface becomes reorganized and forms "sticky patches" when they get close to cancer cells. These new binding geometries have the potential to significantly expand the types of cancer cells that can be targeted with therapeutic agents. The project combines this targeting approach with single molecule optical measurements and mathematical modeling, to understand the mechanisms, and inform the design of optimized particles.
Based on promising initial results in selectively targeting and treating cancer cells using drug-carrying nanoparticles, the investigators will explore and understand the behavior of drug-carrying lipid nanoparticles whose surface phase-separates to form "sticky patches" proximally to tumor cells. The underlying hypotheses are that the targeting success lies in the dense concentration of the binding ligands on these patches, and that the transport and binding kinetics of these novel binding geometries give significantly longer binding times resulting in internalization. These hypotheses will be addressed through four specific aims, which include: 1) Using collective measurements, evaluation of the kinetics of effective cell binding (association), dissociation and internalization processes of sticky lipid nanoparticles; 2) Using single molecule optical tracking techniques, evaluation of the lifetime of the nanoparticle-receptor(s) complex, of the number of nanoparticle-associated receptors that lead to cellular internalization of the complex, and of potential co-localization of receptors for each cell-associated nanoparticle; 3) Development, implementation and use of an experimentally informed general computational tool to test the mechanistic hypotheses, to evaluate the relative importance of the physical and chemical attributes of the nanoparticles used, and ultimately to help design them so as to optimally/selectively target otherwise untargetable cancers; and 4) Utilization of the mathematical model to optimize the design of sticky lipid nanoparticles, and to evaluate their efficacy in vitro. The proposed approach introduces an new geometry for nanoparticles to bind otherwise untargetable cancer cells, and has the potential to ultimately improve the quality of life of patients with advanced cancer and extend their life expectancy. Through this activity the investigators will cross-train one Ph.D. student (at Rutgers) with focus on physical chemistry and self-assembly of heterogeneous lipid membranes, and a second Ph.D. student (at Princeton) with focus on multiscale modeling and experimental biophysics optics. An international collaboration with Applied Mathematics in Oxford will involve a third PhD student, who will repeatedly visit Princeton/Rutgers to interact with the PIs. The investigators will integrate this research in their mentoring of undergraduate students, curriculum development and expansion of undergraduate programs. High school student outreach programs already in place will be supported, in addition to the development and dissemination of educational materials highlighting this research. This award is co-funded by the Biomedical Engineering Program in the Chemical, Bioengineering, Environmental and Transport Systems Division; by Mathematical Sciences through the Mathematical Sciences Innovation Incubator Program; and by the Directorate of Mathematical and Physical Sciences through the Office of Multidisciplinary Activities. |
| 资源类型: | 项目
|
| 标识符: | http://119.78.100.158/handle/2HF3EXSE/93908
|
| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
|
|
There are no files associated with this item.
|
| Recommended Citation: | |
Stavroula Sofou. UNS: Collaborative Research: Unique binding geometries: Engineering & Modeling of Sticky Patches on Lipid Nanoparticles for Effective Targeting of Otherwise Untargetable cells. 2014-01-01.
|
|
|