Antifouling Peptide Mimetic Polymers

描述(由申请人提供)：消除或最小化非特定生物分子与材料的相互作用是完善现有和未来生物材料生物性能的重要组成部分，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。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定蛋白质吸附的抗性；以及2)使用这些信息来指导用于控制医疗器械和纳米颗粒疗法的生物污垢的新型防污肽模拟聚合物的设计。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)的防污性能，并将这些类肽用作纳米抗癌治疗药物的组成部分。在第一和第二个目标中，我们将把分子理论与一种通用的合成策略和详细的蛋白质吸附实验测量相结合，以开发新型的抗污肽类化合物。重点将放在拟糖萼类肽(类糖肽)以及N-甲基甘氨酸类类肽(肌氨酸)上。这些类肽作为表面接枝聚合物的性能将进行实验评估，以抵抗非特定蛋白质和细胞污染，以及 这些结果与分子理论的结果将使我们了解化学组成和链结构对污垢阻力的影响。在目标3中，这些类肽将被嫁接到金纳米棒(AuNRs)上，用MUC1抗体修饰，并在体外和体内模型系统中研究抗癌效果。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组成设计，以获得结合表面密度和分布，从而增强细胞对抗MUC1修饰的AuNRs的摄取。体外研究将利用AuNRs的近红外等离子体特性来探索糖肽的生物相容性、细胞靶向效率和光热细胞消融。最后，一个异种移植瘤模型将被用来展示抗MUC1修饰的AuNRs作为一种新的癌症治疗策略的有效性。

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.