CAREER: Engineering Plasmonic Nanoantenna Architectures for Efficient Nuclear Delivery & Advancing Awareness in Nanotechnology

该职业计划旨在开发可配置的基因传递纳米结构。基因治疗最终依赖于在不暴露邻近细胞的情况下有效地将经过校正的基因传递到细胞膜并最终到达细胞核。该计划配置纳米结构，以有效地和特异性地将基因传递到细胞核。特别是，具有独特光学特性的不对称结构将被开发成光学穿透膜，通过拥挤的细胞内空间光学运输基因，并将基因直接传递到细胞核。有效和特异的基因传递可以降低所需的剂量，并最大限度地减少不必要的副作用。这种策略也提供了一种新的基因传递系统，它可以在传递后光学移除，消除基因传递系统本身的潜在副作用。作为更广泛的影响和推广活动的一部分，该计划旨在提高对纳米技术的认识，并增加未被充分代表的STEM参与。根据这项拟议的研究，实验室课程模块将在研究生阶段设计，研究职业系列将在本科阶段实施，纳米技术顶点研讨会将设计用于吸引K-12学生参与STEM。这些综合活动形成了一个框架，将PI的职业生涯中的研究、教育和推广结合在一起。本职业计划旨在解决基因传递系统面临的挑战，将基因有效和特异性地传递到细胞核。提出的工作将开发等离子纳米天线结构——由不对称配置的纳米颗粒组成——能够光传输、膜穿透和核基因释放，以实现有效的核递送。所提出的研究的智力优势在于等离子体纳米天线结构的配置，显示出高度的不对称性和耦合的纵向模式，以频谱解耦辐射压力的梯度力。梯度力与辐射压力的光谱解耦首次允许在合理的光辐照下的光力，最小化光热诱导的布朗运动，以及在一个波长进行光传输和在另一个波长进行基因释放的光激活的多功能功能。为实现研究目标，需要开展以下工作：(1)确定等离子体纳米天线结构的光输运操作条件。(2)评估与光学不稳定相比，光力穿透是否提高了穿透效率。(3)研究基因释放的空间调节是否会改变基因表达。作为更广泛的影响和推广活动的一部分，该计划旨在提高K-12、本科生和研究生对纳米技术和等离子体动力学的认识，并增加未被充分代表的STEM参与。以下任务有助于实现教育目标：(1)领导顶点研讨会，让K-12学生接触纳米技术。(2)实施研究型职业生涯系列研讨会，以培养对研究感兴趣的本科生作为职业道路。(3)扩大等离子体学研究生课程，纳入实验模块。这些综合活动有助于形成一个框架，将PI的职业生涯中的研究、教育和外联结合起来。

This CAREER plan aims to develop configurable nanostructures for gene delivery. Gene therapyultimately relies on corrected genes to be efficiently delivered across cell membranes and ultimatelyto the cell nucleus without exposing neighboring cells. This plan configures nanostructures todeliver genes efficiently and specifically to the cell nucleus. In particular, asymmetricconfigurations, displaying unique optical properties, will be developed to optically penetratemembranes, optically transport genes through the crowded intracellular space, and deliver genesdirectly to the nucleus. Efficient and specific delivery of corrected genes should lower requireddosages and minimize unwanted side effects. This strategy also offers a new class of gene deliverysystems which can be optically removed post-delivery, eliminating potential side effects from thegene delivery system itself. As part of broader impacts and outreach activities, this plan aims toadvance awareness in nanotechnology, and to increase underrepresented participation in STEM.Drawing from this proposed research, laboratory course modules will be designed at the graduatelevel, research career series will be implemented at the undergraduate level, and nanotechnologycapstone workshops will be designed to engage K-12 students in STEM. These combined activitiesserve to form a framework integrating research, education and outreach over the PI's career.This CAREER plan aims to address the challenge facing gene delivery systems to deliver genesefficiently and specifically to the cell nucleus. The proposed work will develop plasmonicnanoantenna architectures - consisting of asymmetrically configured nanoparticles - capable ofoptical transport, membrane penetration and nuclear gene release for efficient nuclear delivery. Theintellectual merit of the proposed research lies in the configuration of plasmonic nanoantennaarchitectures, displaying high degrees of asymmetry and coupled longitudinal modes, to spectrallydecouple the gradient force from the radiation pressure. Spectral decoupling of the gradient forcefrom the radiation pressure allows, for the first time, optical forces at reasonable light irradiances,minimized photothermally induced Brownian motion, and multi-functional capabilities whereoptical transport is conducted at one wavelength and optical activation of gene release is conductedat another wavelength. The following tasks support the attainment of the research goal: (1) Identifyoperation conditions for optical transport of plasmonic nanoantenna architectures. (2) Assesswhether optical force penetration compared to optical destabilization improves penetrationefficiency. (3) Investigate whether spatial modulation of gene release modifies resulting geneexpression. As part of broader impacts and outreach activities, this plan aims to advance awarenessin nanotechnology and plasmonics at the K-12, undergraduate and graduate level, and to increaseunderrepresented participation in STEM. The following tasks support the attainment of theeducational goal: (1) Lead capstone workshops to expose K-12 students to nanotechnology. (2)Implement research career seminar series to educate undergraduate students interested in researchas a career path. (3) Expand plasmonics graduate course curriculum to include laboratory modules.These combined activities serve to form a framework integrating research, education and outreachover the PI's career.