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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

This CAREER plan aims to develop configurable nanostructures for gene delivery. Gene therapy ultimately relies on corrected genes to be efficiently delivered across cell membranes and ultimately to the cell nucleus without exposing neighboring cells. This plan configures nanostructures to deliver genes efficiently and specifically to the cell nucleus. In particular, asymmetric configurations, displaying unique optical properties, will be developed to optically penetrate membranes, optically transport genes through the crowded intracellular space, and deliver genes directly to the nucleus. Efficient and specific delivery of corrected genes should lower required dosages and minimize unwanted side effects. This strategy also offers a new class of gene delivery systems which can be optically removed post-delivery, eliminating potential side effects from the gene delivery system itself. As part of broader impacts and outreach activities, this plan aims to advance awareness in nanotechnology, and to increase underrepresented participation in STEM. Drawing from this proposed research, laboratory course modules will be designed at the graduate level, research career series will be implemented at the undergraduate level, and nanotechnology capstone workshops will be designed to engage K-12 students in STEM. These combined activities serve 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 genes efficiently and specifically to the cell nucleus. The proposed work will develop plasmonic nanoantenna architectures - consisting of asymmetrically configured nanoparticles - capable of optical transport, membrane penetration and nuclear gene release for efficient nuclear delivery. The intellectual merit of the proposed research lies in the configuration of plasmonic nanoantenna architectures, displaying high degrees of asymmetry and coupled longitudinal modes, to spectrally decouple the gradient force from the radiation pressure. Spectral decoupling of the gradient force from the radiation pressure allows, for the first time, optical forces at reasonable light irradiances, minimized photothermally induced Brownian motion, and multi-functional capabilities where optical transport is conducted at one wavelength and optical activation of gene release is conducted at another wavelength. The following tasks support the attainment of the research goal: (1) Identify operation conditions for optical transport of plasmonic nanoantenna architectures. (2) Assess whether optical force penetration compared to optical destabilization improves penetration efficiency. (3) Investigate whether spatial modulation of gene release modifies resulting gene expression. As part of broader impacts and outreach activities, this plan aims to advance awareness in nanotechnology and plasmonics at the K-12, undergraduate and graduate level, and to increase underrepresented participation in STEM. The following tasks support the attainment of the educational goal: (1) Lead capstone workshops to expose K-12 students to nanotechnology. (2) Implement research career seminar series to educate undergraduate students interested in research as 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 outreach over the PI's career.