CAREER: Biomimetic Self-assembly of Polymer-inorganic Hybrid Nanocompartments with Biomedical Delivery Applications

技术综述：创新的功能杂化纳米材料可能为人类健康提供新一代高度选择性和有效的治疗和诊断方法。该奖项的目标是通过聚合物辅助的纳米颗粒自组装合成一类新型的聚合物-无机泡囊杂化药物。这些功能性囊泡杂交物从大小、表面贴片、表面拓扑结构和机械性能等方面模仿病毒衣壳，从而促进了其在医疗输送中的功能。组件中的每个聚合物系留纳米颗粒的积木都充当聚合物砖，在纳米尺度上唯一地定义泡状杂化物膜表面上的局部物理和化学线索。这一策略能够制备具有生物医学输送所需关键特征的囊状杂化材料，包括(1)量身定制的渗透性、表面官能度、表面拓扑和机械性能，(2)由于无机纳米颗粒在组装件中的有序性和重量分数显著提高，(2)无机组分的固有或新的协同性能可调，(3)除了成像和操作能力外，还可远程控制包裹物的释放，同时保持聚合物配体原有的独特功能。该建议的目标是：(1)在纳米尺度上了解和控制具有明确可调表面贴片、表面拓扑和机械性能的囊状杂化材料的构建；(2)设计对包括pH、温度、光和潜在电磁场在内的外部刺激的响应的多室泡囊杂化材料和系统；(3)探索药物化合物在囊状杂化材料中的包封性，并研究遥控释放货物的动力学。非技术综述：聚合物-无机杂化纳米隔间具有高度组织化、拓扑结构复杂的表面，从医疗保健和医学(例如，成像造影剂和药物输送囊泡)到光电子学都有重要的应用。拟议的计划将开发新的强大的多功能混合隔间，以应对目前生物医学输送方面的挑战，探索一类新型远程控制响应材料，并为聚合物辅助无机纳米颗粒的自组装提供新的见解。该奖项将允许PI将仿生聚合物-无机杂化材料的跨学科研究与研究生、本科生和高中学生的教育相结合。其目标是使学生在学术界和工业界都具有竞争优势，并帮助他们成为这些新的和新兴的研究领域的领导者。拟议的外展计划旨在：i)将新兴研究领域的当前进展纳入课程开发，如研究生和本科生的实验室设计；ii)招收和培训学生，特别是研究生和本科生中代表性不足的群体；iii)创建一个针对感兴趣的高中生的辅导计划；以及iv)将先进的教育科学演示带到课堂上。

TECHNICAL SUMMARY:Innovative functional hybrid nanomaterials may offer a new generation of highly selective and effective therapeutics and diagnostics for human health. The goal of this award is to synthesize a new class of polymer-inorganic vesicular hybrids for drug delivery through polymer-assisted nanoparticle self-assembly. These functional vesicular hybrids mimic viral capsids from the aspects of size, surface patch, surface topology, and mechanical properties, thus facilitating their functions in medical delivery. Each building block of polymer-tethered nanoparticles in the assemblies serves as a polymeric brick to uniquely define the local physical and chemical cues on the membrane surface of vesicular hybrids at the nanoscale. This strategy enables the preparation of vesicular hybrids with critical features required by biomedical delivery, including (1) tailored permeability, surface functionality, surface topology, and mechanical properties, (2) tunable inherent or new synergetic properties of inorganic components due to significantly enhanced ordering and weight fraction of inorganic nanoparticles in the assemblies, (3) remote-controlled release of encapsulated cargo in addition to imaging and manipulation capability while preserving the original unique functionalities of the polymer ligands. The objectives of this proposal are: (1) to understand and control the construction of vesicular hybrids with well-defined tunable surface patches, surface topology, and mechanical properties at the nanoscale; (2) to design multicompartment vesicular hybrids and systems that respond to external stimuli including pH, temperature, light, and potentially electromagnetic field; (3) to explore the encapsulation of drug compounds in vesicular hybrids and study the kinetics of remote-controlled release of cargo. NON-TECHNICAL SUMMARY:Polymer-inorganic hybrid nanocompartments with highly organized, topologically complex surfaces have important applications ranging from healthcare and medicine (e.g., imaging contrast agents and drug delivery vesicles) to optoelectronics. The proposed program will develop new robust multifunctional hybrid compartments to address current challenges in biomedical delivery, explore a new class of remote-controlled responsive materials, and provide new insights into polymer-assisted self-assembly of inorganic nanoparticles. This award will allow the PI to integrate interdisciplinary research on biomimetic polymer-inorganic hybrids with education of students at the graduate, undergraduate, and high-school levels. The goal is to give students a competitive edge in both academia and industry, and to help them become leaders in these new and emerging research fields. The proposed outreach program seeks to: i) incorporate current advances in emerging research fields into curriculum development such as laboratory design at both graduate and undergraduate levels, ii) recruit and train students particularly under-represented groups at both graduate and undergraduate levels, iii) create a mentoring program aimed at interested high school students, and iv) bring advanced educational science demonstrations to classrooms.