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

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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.