Hierarchical Assembly of Liposomes with Shape-Controlled Metal Nanoparticles for Multifunctional Theranostics

同时能够靶向诊断疾病和递送治疗药物的多功能纳米颗粒对于在单一程序中实现高度特异性的疾病检测和治疗具有重要意义。 在这项工作中，一个单一的多功能纳米粒子，脂质纳米天线，将纳米制造的联合治疗和诊断（治疗诊断学）在癌细胞。Lipo-Nanoantennas将最终促进临床适用的技术，该技术可以从“工作台到床边”转换，从而允许以高精度对癌症生物标志物进行微创成像。脂质纳米天线还将同时提供剂量控制治疗，最大限度地减少与化疗相关的脱靶毒性。 此外，脂质纳米天线可以允许早期检测和靶向治疗多种疾病，包括心血管和传染病。 项目目标的成功实施将最终使我们能够生成一个功能性纳米材料组件库，这些组件将影响多种技术，包括传感，催化和自修复涂层。值得注意的是，该项目还建立了PI的研究和核心本科化学工程课程之间的接口，PI教授药物输送实验室。此外，这项工作将增加PI实验室研究生和本科生中代表性不足的少数民族的参与，并推动K-12学生中基于研究的外展活动。该奖项的目的是研究热敏脂质体与金纳米天线（Lipo-Nanoantennas）的分层组装，以实现多功能治疗诊断。 这将利用定向自组装，一种自下而上的纳米制造方法，提供对材料特性的纳米级控制，这对增强治疗诊断学至关重要。脂质体是临床批准的药物载体，纳米天线非常适合成像和将近红外光转换为热量。纳米天线产生的热量被脂质体吸收，破坏脂质双层并触发药物释放。脂质纳米天线的定向组装提供了纳米制造结构的机械设计，其可以直接在药物释放点利用强烈的光热响应。 这产生了高效的光热药物递送，具有最小的脱靶毒性和精确的细胞成像，所有这些都具有单个纳米级实体。通过控制脂质体内金纳米结构的装载密度和形状，以及它们的总体尺寸和材料特性，将操纵Lipo-Nanoantennas的光热响应，以促进细胞中增强的摄取、成像和药物释放。然后，脂质纳米天线将用于表面增强拉曼成像和癌细胞中化疗药物的递送。我们的中心假设是，理解脂质纳米天线的定向组装将提供一种相对于其他方法的变革性方法，该方法将同时实现上级生物物理特性和治疗诊断学。

Multifunctional nanoparticles that simultaneously enable targeted diagnosis of a disease and delivery of a therapeutic drug are of significant interest to achieving highly specific disease detection and treatment in a single procedure. In this work a single multifunctional nanoparticle, Lipo-Nanoantennas, will be nanomanufactured for combined therapeutics and diagnostics (theranostics) in cancer cells. Lipo-Nanoantennas will ultimately facilitate a clinically applicable technology which can be translated from "bench to bedside" allowing minimally invasive imaging of cancer biomarkers with high precision. Lipo-Nanoantennas will also simultaneously deliver dose-controlled treatment minimizing off-target toxicities associated with chemotherapy. Further, Lipo-Nanoantennas may allow early detection and targeted treatment of multiple diseases including cardiovascular and infectious diseases. Successful implementation of the project goals will ultimately enable us to generate a library of functional nanomaterial assemblies that will impact multiple technologies including sensing, catalysis, and self-healing coatings. Notably, this project also builds an interface between the PI's research and core undergraduate chemical engineering curriculum where the PI teaches a drug delivery laboratory. Further, this work will increase participation of underrepresented minorities at the graduate and undergraduate level in the PI's lab, and propel research-based outreach activities among K-12 students.The objective of this award is to study the hierarchical assembly of thermosensitive liposomes with gold nanoantennas (Lipo-Nanoantennas) to enable multifunctional theranostics. This will leverage directed self-assembly, a bottom-up nanomanufacturing approach, that offers nanoscale control of material properties critical to enabling enhanced theranostics. Liposomes are clinically-approved drug carriers and nanoantennas are ideally suited for both imaging and converting near-infrared light to heat. Heat generated by the nanoantennas is absorbed by the liposomes disrupting the lipid bilayer and triggering drug release. Directed assembly of Lipo-Nanoantennas provides a mechanistic design of a nanomanufactured construct that can leverage intense photothermal response directly at the point of drug release. This gives rise to highly efficient photothermal drug delivery with minimal off-target toxicity and precise cellular imaging all with a single nanoscale entity. By controlling the loading density and shape of gold nanostructures within the liposomes, and their overall size and material properties, the photothermal response of Lipo-Nanoantennas will be manipulated to promote enhanced uptake, imaging, and drug release in cells. The Lipo-Nanoantennas will then be utilized for surface-enhanced Raman imaging and delivery of chemotherapeutic drugs in cancer cells. Our central hypothesis is that understanding directed-assembly of Lipo-Nanoantennas will offer a transformative approach relative to other methods that will simultaneously enable superior biophysical properties, and theranostics.