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Title page for ETD etd-03242017-115848


Type of Document Dissertation
Author Beavers, Kelsey Ross
URN etd-03242017-115848
Title Engineering Porous Silicon Nanoparticles for Delivery of Peptide Nucleic Acid Therapeutics
Degree PhD
Department Interdisciplinary Materials Science
Advisory Committee
Advisor Name Title
Craig L. Duvall, Ph.D. Committee Chair
Sharon M. Weiss, Ph.D., M.S. Committee Co-Chair
David W. Wright, Ph.D. Committee Member
Jeremy W. Mares, Ph.D. Committee Member
Kasey C. Vickers, Ph.D. Committee Member
Raymond L. Mernaugh, Ph.D. Committee Member
Todd D. Giorgio, Ph.D. Committee Member
Keywords
  • drug delivery
  • porous silicon
  • nanoparticle
  • miRNA
  • peptide nucleic acid
  • anti-miRNA
Date of Defense 2016-07-29
Availability restrictone
Abstract
Researchers discovered the existence of non-coding RNA while unraveling the secrets of the human genome. Non-coding RNA molecules are never translated into proteins, yet they are highly abundant and serve critical functions within all cells. Imbalances in one class of regulatory non-coding RNA, known as microRNA (miRNA), lead to diseases such as cancer and cardiovascular disease. MiRNA inhibition is a potent therapeutic strategy because single miRNAs can regulate hundreds of different disease-associated genes. Peptide nucleic acids (PNA) are excellent miRNA inhibitors, yet they have no innate ability to reach miRNA targets in the body. This works’ central hypothesis is that therapeutic anti-miRNA activity can be improved by engineering nanoparticles to increase PNA blood circulation half-life, cellular uptake, and targeted delivery to the cytoplasm of diseased cells. In this thesis, two highly tunable biomaterials (porous silicon and “smart” polymers) are combined to form composite nanoparticles that improve the PNA therapeutic delivery. These nanocomposites are shown to be non-toxic, increase PNA blood-circulation half-life from <1 min to 70 min, and improve PNA delivery to its site of action in target cells. This thesis demonstrates how nanotechnology can aid the clinical translation of a promising new class of therapeutics.
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