Antifouling Peptide Mimetic Polymers

防污肽模拟聚合物

• 批准号: 8724495
• 负责人: Phillip B Messersmith
• 金额: $ 33.1万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 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/8724495
• 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

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进现有和未来生物材料生物性能的一个组成部分，因为表面的生物污垢会导致设备性能受损，成本增加，以及患者的健康问题。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、靶向和整体性能方面发挥着重要作用。本研究的长期目标是：1)了解围绕工程表面与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抗性；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垢。为了实现这一目标，我们将结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，并将这些类肽作为纳米颗粒抗癌治疗的一个组成部分。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，以开发新的抗污染肽。重点将是糖萼类肽（糖肽类），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来评估其对非特异性蛋白质和细胞污垢的抗性，以及整合