权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Antifouling Peptide Mimetic Polymers

防污肽模拟聚合物

基本信息

批准号：
8578748
负责人：
Phillip B Messersmith
金额：
$ 34.15万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8578748
关键词：
Ablation Adsorption Alanine Animal Model Antibodies Architecture Behavior Binding Biocompatible Materials Biodistribution Biological Biological Models Biomimetics Biosensor Blood Breast Cancer Cell Cardiovascular system Cell Communication Cell physiology Cells Characteristics Chemicals Chemistry Complex Contact Lenses Coupled Development Devices Diagnostic Emerging Technologies Engineering Epithelial Experimental Designs Future Glycocalyx Goals Gold Health Care Costs Healthcare In Vitro Indwelling Catheter Investigation Lead Length Ligands Malignant Neoplasms Measurement Medical Device Membrane Proteins Methods Modeling Molecular Molecular Weight Mucin-1 Staining Method Mucins N-substituted Glycines Outcomes Research Patients Peptides Peptoids Performance Phase Play Polymers Property Proteins Research Resistance Role Sarcosine Side Solid Surface Technology Theoretical Studies Therapeutic Tissues Xenograft procedure anti-cancer therapeutic base biomaterial compatibility cancer cell cancer therapy density design improved in vivo in vivo Model innovation insight interfacial mimetics molecular dynamics nanomaterials nanomedicine nanoparticle nanorod novel novel strategies overexpression particle peptide analog plasmonics prevent programs public health relevance research study subcutaneous success theories tumor xenograft uptake

项目摘要

DESCRIPTION (provided by applicant): The elimination or minimization of nonspecific biomolecule-material interactions is an integral part of refining the biological performance of existing and future biomaterials, as biofouling of surfaces can lead to compromised device performance, increased cost, and health concerns for the patient. In the emerging field of nanomedicine, for example, biointerfacial interactions play an important role in biodistribution, targeting and overall performance of nanomaterials. The long-term goals of this research are 1) to understand the fundamental biointerfacial phenomena surrounding interactions between engineered surfaces and biomolecules, with a specific emphasis on resistance of grafted polymers to nonspecific protein adsorption; and 2) to use this information to guide the design of novel antifouling peptide mimetic polymers for use in controlling biofouling of medical devices and nanoparticle therapeutics. To accomplish this, we will integrate experimental and theoretical approaches to study the antifouling properties of N-substituted glycine polymers (peptoids), and employ these peptoids as an integral component of a nanoparticle anticancer therapeutic. In the first and second aims, we will combine molecular theory with a versatile synthetic strategy and detailed experimental measurements of protein adsorption to develop novel antifouling peptoids. The focus will be on glycocalyx-mimetic peptoids (glycopeptoids), as well as N-methylglycine peptoid (sarcosine). The performance of these peptoids as surface-grafted polymers will be experimentally evaluated for resistance to nonspecific protein and cell fouling, and integration of these results with those obtained by molecular theory will allow us to understand the effects of chemical composition and chain architecture on fouling resistance. In Aim 3, these peptoids will be grafted onto gold nanorods (AuNRs), modified with MUC1 antibody and investigated for anticancer efficacy in in-vitro and in-vivo model systems. An innovative aspect of this aim involves the use of theoretical predictions to guide the architectural and compositional design of peptoids to achieve bound surface densities and distributions that enhance the cellular uptake of anti-MUC1 modified AuNRs. In-vitro studies will probe glycopeptoid biocompatibility, cell-targeting efficiency, and photothermal cell ablation using the near-infrared plasmonic properties of the AuNRs. Finally, a xenograft tumor model will be used to demonstrate the efficacy of the anti-MUC1 modified AuNRs as a novel strategy for cancer therapy.

描述（由申请人提供）：消除或最小化非特异性生物分子-材料相互作用是改善现有和未来生物材料的生物性能的一个组成部分，因为表面的生物污垢可能会导致设备性能受损、成本增加和患者健康问题。例如，在新兴的纳米医学领域，生物界面相互作用在纳米材料的生物分布、靶向和整体性能中发挥着重要作用。这项研究的长期目标是 1) 了解围绕工程表面和生物分子之间相互作用的基本生物界面现象，特别强调接枝聚合物对非特异性蛋白质吸附的抵抗力； 2）利用这些信息来指导新型防污肽模拟聚合物的设计，用于控制医疗器械和纳米颗粒疗法的生物污染。为了实现这一目标，我们将整合实验和理论方法来研究 N-取代甘氨酸聚合物（类肽）的防污特性，并将这些类肽用作纳米颗粒抗癌治疗的组成部分。在第一个和第二个目标中，我们将把分子理论与多功能合成策略和蛋白质吸附的详细实验测量相结合，以开发新型防污类肽。重点是糖萼模拟类肽（糖肽）以及 N-甲基甘氨酸类肽（肌氨酸）。这些类肽作为表面接枝聚合物的性能将通过实验评估，以抵抗非特异性蛋白质和细胞污染，以及整合这些结果与分子理论获得的结果将使我们能够了解化学成分和链结构对防污性的影响。在目标 3 中，这些拟肽将被移植到金纳米棒 (AuNR) 上，用 MUC1 抗体进行修饰，并在体外和体内模型系统中研究其抗癌功效。这一目标的一个创新方面涉及使用理论预测来指导类肽的结构和成分设计，以实现结合表面密度和分布，从而增强细胞对抗 MUC1 修饰的 AuNR 的摄取。体外研究将利用 AuNR 的近红外等离子体特性来探讨糖肽生物相容性、细胞靶向效率和光热细胞消融。最后，异种移植肿瘤模型将用于证明抗 MUC1 修饰的 AuNR 作为癌症治疗新策略的功效。