Logic-gated pro-MMP activation for tumor-specific motility in nanocarriers
纳米载体中肿瘤特异性运动的逻辑门控 MMP 前体激活
基本信息
- 批准号:2220667
- 负责人:
- 金额:$ 52.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-15 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Nanoparticles deliver anti-cancer drugs to tumors. They prevent exposure of the rest of the body to these toxic drugs. Penetrating the tumor is difficult. Understanding the factors that govern the behavior of drug nanocarriers within the tumor could help improve delivery. One strategy to improve delivery has been to try digesting the matrix material surrounding tumors. The enzymes used are referred to as matrix metalloproteinases (MMPs). Unfortunately, MMPs can be toxic to surrounding cells and tissue. The major objective of this research is to create ‘smart’ MMPs whose activity is specific for tumor matrix material only. Outreach and educational efforts are designed to attract students to careers in engineering and improve technological literacy. Pre-college research internships, drug delivery teaching modules for a local middle school, and new course modules in protein engineering and drug delivery are planned.Nanocarriers offer numerous potential benefits in drug delivery. These include their abilities to precisely target drug delivery, to control release, extend circulation time within the body, and offer stimulus-responsive features. Poor penetration caused by the features of the tumor stroma/matrix is cited as a primary challenge to drug delivery effectiveness. This project fuses diverse expertise in synthetic biology/protein engineering and drug delivery/biomaterials to create tumor-actuatable pro-MMPs and uncover mechanisms governing their site-selective unmasking, proteolytic activity, and capacity to enhance nanocarrier transport within tumor-relevant extracellular matrix. Certain MMPs (MMP-9 for example) have elevated concentrations in tumor microenvironments. Synthetic pro-MMPs that are conditionally activated by the elevated MMPs will be designed. The ability of these conditional pro-MMPs to provide MMP-specific mobility enhancements to protein nanostructures will be evaluated.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
纳米颗粒将抗癌药物输送到肿瘤,但了解控制药物纳米载体在肿瘤内的行为的因素可能有助于改善输送。改善递送一直是尝试消化肿瘤周围的基质材料,不幸的是,MMP 可能对周围的细胞和组织有毒。 “智能”MMP 的活动仅针对肿瘤基质材料,旨在吸引学生从事工程职业并提高大学预科研究实习、当地中学的药物输送教学模块和新的课程。计划开设蛋白质工程和药物输送方面的课程模块。纳米载体在药物输送方面具有许多潜在的好处,包括精确靶向药物输送、控制释放、延长体内循环时间以及提供刺激响应特性的能力。造成的肿瘤基质/基质的特征被认为是药物输送有效性的主要挑战,该项目融合了合成生物学/蛋白质工程和药物输送/生物材料方面的多种专业知识,以创建肿瘤可驱动的 MMP 前体并揭示其位点的调控机制。 -选择性揭示、蛋白水解活性和增强肿瘤相关细胞外基质内纳米载体转运的能力某些 MMP(例如 MMP-9)在肿瘤微环境中浓度升高。将设计由 MMP 有条件激活的 pro-MMP。将对这些有条件的 pro-MMP 为蛋白质纳米结构提供 MMP 特异性迁移增强的能力进行评估。该奖项反映了 NSF 崇高的法定使命,并被认为值得支持。通过使用基金会的智力优点和更广泛的影响审查标准进行评估。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Wilfred Chen其他文献
Temperature-triggered purification of antibodies.
温度触发的抗体纯化。
- DOI:
10.1002/bit.20451 - 发表时间:
2005-05-05 - 期刊:
- 影响因子:3.8
- 作者:
Jae;A. Mulch;ani;ani;Wilfred Chen - 通讯作者:
Wilfred Chen
Functional assembly and characterization of a modular xylanosome for hemicellulose hydrolysis in yeast
用于酵母半纤维素水解的模块化木糖体的功能组装和表征
- DOI:
10.1002/bit.24609 - 发表时间:
2013-01-01 - 期刊:
- 影响因子:3.8
- 作者:
S. Srikrishnan;Wilfred Chen;N. D. Da Silva - 通讯作者:
N. D. Da Silva
Tunable Biopolymers for Heavy Metal Removal
用于去除重金属的可调节生物聚合物
- DOI:
10.1021/ma001973m - 发表时间:
2001-03-02 - 期刊:
- 影响因子:5.5
- 作者:
J. Kostal;A. Mulch;ani;ani;Wilfred Chen - 通讯作者:
Wilfred Chen
Genetically engineered bio-nanoparticles with co-expressed enzyme reporter and recognition element for IgG immunoassay
具有共表达酶报告基因和 IgG 免疫测定识别元件的基因工程生物纳米颗粒
- DOI:
10.1016/j.snr.2019.100003 - 发表时间:
2019-12-01 - 期刊:
- 影响因子:0
- 作者:
Yikun Huang;Haomin Liu;Wilfred Chen;M. Nieh;Yu Lei - 通讯作者:
Yu Lei
Sensitive and Selective Electrochemical Biosensor Based on ELP-OPH/BSA/TiO2NFs/AuNPs for Determination of Organophosphate Pesticides withp-Nitrophenyl Substituent
基于ELP-OPH/BSA/TiO2NFs/AuNPs的灵敏选择性电化学生物传感器测定对硝基苯基取代基有机磷农药
- DOI:
10.1149/2.0311702jes - 发表时间:
2024-09-14 - 期刊:
- 影响因子:3.9
- 作者:
Jing Bao;Changjun Hou;D. Huo;Qiuchen Dong;Xiaoyue Ma;Xiangcheng Sun;Mei Yang;K. Galil;Wilfred Chen;Yu Lei - 通讯作者:
Yu Lei
Wilfred Chen的其他文献
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{{ truncateString('Wilfred Chen', 18)}}的其他基金
Collaborative Research: NSF/MCB: Repurposing metabolite-responsive aptamers for real-time sensing and dynamic control of Cas6-mediated metabolon assembly
合作研究:NSF/MCB:重新利用代谢物响应适体,用于 Cas6 介导的代谢物组装的实时传感和动态控制
- 批准号:
2317398 - 财政年份:2023
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Collaborative Research: Synthetic methane fixation cascades based on engineered membrane vesicles for biofuel cell applications
合作研究:基于工程膜囊泡的合成甲烷固定级联,用于生物燃料电池应用
- 批准号:
2221893 - 财政年份:2022
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Rapid purification of recombinant proteins by protein nanoparticle crosslinking and light-responsive nanobodies
通过蛋白质纳米颗粒交联和光响应纳米抗体快速纯化重组蛋白
- 批准号:
2040749 - 财政年份:2021
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Collaborative Research: Synthetic CRISPR-Cas6 endonucleases for dynamic control of cellular phenotypes in yeast
合作研究:用于动态控制酵母细胞表型的合成 CRISPR-Cas6 核酸内切酶
- 批准号:
2013991 - 财政年份:2020
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Collaborative Research: Redirecting cellular metabolism via synthetic toehold-gated dCas9 regulators
合作研究:通过合成的门控 dCas9 调节器重定向细胞代谢
- 批准号:
1817675 - 财政年份:2018
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Collaborative Research: Dynamic degradation of proteins by ubiquitination provides a novel therapeutic for controlling elevated protein levels
合作研究:通过泛素化动态降解蛋白质为控制蛋白质水平升高提供了一种新的治疗方法
- 批准号:
1803008 - 财政年份:2018
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Biochemical and Molecular Engineering XX Conference
生化与分子工程XX会议
- 批准号:
1739060 - 财政年份:2017
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
Repurposing the CRISPR-Cas9 system for dynamic control of cellular metabolism
重新利用 CRISPR-Cas9 系统动态控制细胞代谢
- 批准号:
1615731 - 财政年份:2016
- 资助金额:
$ 52.1万 - 项目类别:
Continuing Grant
Design of Multi-Functional SplitCore HBV Capsids for Precisely Controlled Multi-siRNA Delivery in Cancer Therapeutics
设计多功能 SplitCore HBV 衣壳,用于癌症治疗中精确控制的多 siRNA 递送
- 批准号:
1609621 - 财政年份:2016
- 资助金额:
$ 52.1万 - 项目类别:
Continuing Grant
Collaborative Research: Advanced biomanufacturing of functional bionanoparticles for biomedical engineering applications
合作研究:用于生物医学工程应用的功能性生物纳米颗粒的先进生物制造
- 批准号:
1604925 - 财政年份:2016
- 资助金额:
$ 52.1万 - 项目类别:
Standard Grant
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