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Publication Date

2024-5

First Advisor

Nathan D. Derr

Second Advisor

David J. Gorin

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Chemistry

Keywords

DNA origami, lipid nanoparticles, nanotechnology, targeted therapeutics

Abstract

Nanotechnology has emerged as a powerful tool for targeted drug delivery through its ability to encapsulate, protect, and deliver a variety of therapeutic agents. A cutting-edge technique for targeted drug delivery on the nanoscale is DNA origami (DNA-O), which allows precise structures to be created and functionalized. These functionalizations can result in stimulus-responsive conformational changes to the DNA-O structure, resulting in payload release. Here, a suite of DNA-O exoskeletons and cationic lipid or polymer-based cores are conceptualized, designed, and developed for the creation of two distinct layered targeted delivery vehicles. These structures include (a) a 42 nm DNA-O exoskeleton for encapsulating (b) a polyethyleneimine (PEI)-wrapped gold nanoparticle (AuNP) as well as (c) a 115 nm DNA-O exoskeleton for encapsulating either (d) a lipid nanoparticle core or (e) a core of PEI complexed with DNA. The 42 nm DNA-O exoskeleton is based on previous work from the Derr Lab and has two tethered hemispheres and has been further modified to include thiol handles intended to reversibly close the sphere through disulfide bond formation. PEI-AuNPs were successfully wrapped, cationic, and ≤ 40 nm, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The 115 nm DNA-O structure was modeled and DNA sequences were designed for folding one hemisphere. LNPs were synthesized with microfluidics and LNPs and PEI-DNA polyplexes were both characterized and confirmed to be ≤ 115 nm and cationic using DLS and TEM. Collectively, these results present a toolkit designed for creating layered nanostructures that could be used for the encapsulation of therapeutics and targeted drug delivery.

Rights

©2024 Justine Wagaman. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

Comments

109 pages: color illustrations, charts. Includes bibliographical references (pages 72-84).

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