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递送到肿瘤。它们可以防止身体其他部位接触这些有毒药物。穿透肿瘤很困难。了解控制肿瘤内药物纳米载体行为的因素可以帮助改善递送。改善递送的一种策略是尝试消化肿瘤周围的基质材料。所使用的酶被称为基质金属蛋白酶(MMP)。不幸的是,MMPs可能对周围的细胞和组织有毒。 本研究的主要目的是创造“智能”MMPs,其活性仅对肿瘤基质材料具有特异性。 外联和教育工作旨在吸引学生从事工程职业并提高技术素养。大学预科研究实习,当地中学的药物输送教学模块,以及蛋白质工程和药物输送的新课程模块正在计划中。纳米载体在药物输送方面提供了许多潜在的好处。这些包括它们精确靶向药物递送、控制释放、延长体内循环时间以及提供刺激响应特征的能力。由肿瘤基质/基质的特征引起的渗透性差被认为是药物递送有效性的主要挑战。该项目融合了合成生物学/蛋白质工程和药物递送/生物材料方面的各种专业知识,以创建肿瘤致动的pro-MMPs,并揭示其位点选择性解蔽,蛋白水解活性和增强肿瘤相关细胞外基质内纳米载体运输的能力的机制。 某些MMP(例如MMP-9)在肿瘤微环境中具有升高的浓度。将设计由升高的MMP条件性激活的合成MMP原。这些有条件的前基质金属蛋白酶的能力,提供基质金属蛋白酶特定的流动性增强蛋白质nanostructures.This奖项反映了NSF的法定使命,并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。
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
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 - 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
Engineering a high‐affinity scaffold for non‐chromatographic protein purification via intein‐mediated cleavage
通过内含肽介导的切割设计用于非层析蛋白质纯化的高亲和力支架
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:3.8
- 作者:
Fang Liu;Shen;Bhawna Madan;Wilfred Chen - 通讯作者:
Wilfred Chen
Peptide-Delivered Molecular Beacons Poliovirus-Infected Cells via TAT Quantitative Detection of Use of Flow Cytometry for Rapid
通过 TAT 快速定量检测流式细胞仪对脊髓灰质炎病毒感染细胞进行肽递送分子信标
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
M. Yates;Wilfred Chen;D. Sivaraman;Hsiao;A. Mulchandani - 通讯作者:
A. Mulchandani
High‐efficiency affinity precipitation of multiple industrial mAbs and Fc‐fusion proteins from cell culture harvests using Z‐ELP‐E2 nanocages
使用 Z-ELP-E2 纳米笼对细胞培养物中的多种工业 mAb 和 Fc 融合蛋白进行高效亲和沉淀
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:3.8
- 作者:
A. Swartz;Xuankuo Xu;Steven J Traylor;Z. Li;Wilfred Chen - 通讯作者:
Wilfred Chen
Customizable Biopolymers for Heavy Metal Remediation
用于重金属修复的可定制生物聚合物
- DOI:
10.1007/s11051-005-5132-y - 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
J. Kostal;G. Prabhukumar;U. L. Lao;Alin Chen;M. Matsumoto;A. Mulchandani;Wilfred Chen - 通讯作者:
Wilfred Chen
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: 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
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
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
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
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
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