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

创新的功能性杂化纳米材料可以为人类健康提供新一代高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纳米颗粒自组装合成一类新的聚合物-无机囊泡杂化物用于药物递送。这些功能性囊泡杂交体从大小、表面补丁、表面拓扑和机械性质方面模拟病毒衣壳，从而促进其在药物递送中的功能。组装体中的聚合物束缚的纳米颗粒的每个构建块充当聚合物砖，以在纳米尺度下独特地限定囊泡混合物的膜表面上的局部物理和化学线索。 该策略使得能够制备具有生物医学递送所需的关键特征的囊泡杂化物，所述关键特征包括（1）定制的渗透性、表面功能性、表面拓扑结构和机械性质，（2）由于组装体中无机纳米颗粒的显著增强的有序性和重量分数而导致的无机组分的可调节的固有或新的协同性质，（3）除了成像和操作能力之外，还可以远程控制释放包封的货物，同时保留聚合物配体的原始独特功能。本研究的目标是：（1）理解和控制泡状杂交体的构建，其具有明确的可调表面补丁、表面拓扑结构和纳米级的机械性能;（2）设计多室泡状杂交体和系统，其对外部刺激（包括pH、温度、光和潜在的电磁场）作出响应;（3）探索药物在囊泡复合体中的包封和货物的远程控制释放动力学。非技术概述：具有高度组织化的、拓扑复杂的表面的聚合物-无机杂化纳米隔室具有重要的应用，其范围从医疗保健和医学（例如，成像造影剂和药物递送囊泡）到光电子学。该计划将开发新的强大的多功能混合隔间，以应对当前生物医学输送的挑战，探索一类新的远程控制响应材料，并为无机纳米粒子的聚合物辅助自组装提供新的见解。该奖项将允许PI将仿生聚合物-无机混合物的跨学科研究与研究生，本科和高中水平的学生教育相结合。我们的目标是让学生在学术界和工业界的竞争优势，并帮助他们成为这些新的和新兴的研究领域的领导者。拟议的推广计划旨在：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）招募和培训学生，特别是在研究生和本科生两个层次的代表性不足的群体，iii）创建一个针对感兴趣的高中生的辅导计划，iv）将先进的教育科学示范带到教室。

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.