title: Functionally-interdependent shape-switching nanoparticles with controllable properties.
abstract: We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities. Computational algorithms were developed to accurately predict melting temperatures of nanoparticles of various compositions and trace the process of their re-association in silico. Additionally, tunable immunostimulatory properties of described nanoparticles suggest that the particles that do not induce pro-inflammatory cytokines and high levels of interferons can be used as scaffolds to carry therapeutic oligonucleotides, while particles with strong interferon and mild pro-inflammatory cytokine induction may qualify as vaccine adjuvants. The presented concept provides a simple, cost-effective and straightforward model for the development of combinatorial regulation of biological processes in nucleic acid nanotechnology.
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Halman
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Satterwhite
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Roark
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Chandler
authors.affiliation: RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.|Basic Science Program, Leidos Biomedical Research, Inc., RNA Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Viard
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Ivanina
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc., RNA Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Eckart
authors.initials: E
authors.lastname: Bindewald
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc., RNA Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Wojciech K
authors.initials: WK
authors.lastname: Kasprzak
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik University in Kosice, Kosice, 041 54, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Panigaj
authors.affiliation: Department of Chemistry, Ball State University, Muncie, IN 47306, USA.
authors.forename: My N
authors.initials: MN
authors.lastname: Bui
authors.affiliation: RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Lu
authors.affiliation: RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Johann
authors.initials: J
authors.lastname: Miller
authors.affiliation: Department of Chemistry, Ball State University, Muncie, IN 47306, USA.
authors.forename: Emil F
authors.initials: EF
authors.lastname: Khisamutdinov
authors.affiliation: RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Shapiro
authors.affiliation: Nanotechnology Characterization Lab, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Dobrovolskaia
authors.affiliation: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.|The Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Afonin
mesh_terms: D052157:Aptamers, Nucleotide; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D021621:Imaging, Three-Dimensional; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D009841:Oligonucleotides / Q000737:chemistry / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D034622:RNA Interference; D013816:Thermodynamics; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D052157:Aptamers, Nucleotide; D016207:Cytokines; D009696:Nucleic Acids; D009841:Oligonucleotides; D012313:RNA; D004247:DNA