JSTO in the news

DTRA.MIL

JSTO in the newsLead DoD science and technology to anticipate, defend, and safeguard against chemical and biological threats for the Warfighter and the Nation.

February 2015 Vol. 5 No. 2

Distribution Statement A. Distribution is unlimited.

Man-made Micromachines in a Mouse’s Stomach: In Vivo Use of Synthetic Motors The first study of synthetic micromotors in vivo (in a living organism) is paving the way for future clinical studies, developing medical countermeasures and other lifesaving applications—ultimately helping to prevent or aid in healing warfighters in harm’s way.

The research project, managed by Dr. Brian Pate of DTRA CB/JSTO, has resulted in ability to introduce artificial micromotors to a living organism. In the study, principal investigators Professor Joseph Wang and Dr. Wei Gao, University of California - San Diego, and their team, loaded gold nanoparticles (AuNPs) onto zinc (Zn) based micromotors and introduced them to the stomachs of living mice.

Within the hosts the micromotors’ autonomous movement and biodistribution was monitored along with toxicity profiles, gastric tissues retention and delivery rates. Results showed that these self-propelled micromotors dramatically improved payload retention in the stomach lining as compared to the common passive diffusion and dispersion of similar orally administered payloads.

Although AuNPs were selected as model cargo due to their common use as imaging agents and drug carriers, this micromotor platform may be readily expanded to

include the simultaneous encapsulation and rapid delivery of multiple payloads. This approach affords additional capabilities in therapy, diagnostics and imaging applications. Alternative functionalities may be added to these micromotors through bulk or surface modifications to further expand biomedical applications.

Unlike most existing micromotors, Zn-based micromotors destroy themselves upon completing their cargo delivery mission. This is

Understanding Dengue Virus Molecular Basis Key to Enabling New Countermeasures Preventing and countering warfighter exposure to Dengue and other viruses is critical to accomplishing their mission. Currently there are no Dengue virus (DV) vaccines fielded and, because it is necessary to first understand the viral infection process mechanisms,

the ability to develop new tools to counter viral infections is challenging.

Researchers, including principal investigator Susan Rempe, at Sandia National Laboratory, through a project managed by Dr. Brian Pate of DTRA

CB/JSTO, are successfully working to solve this problem.

The team seeks to explain the key physical determinants of selective biomolecule entry into nanopores and better understand the viral infection

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Self-propelled micromotors may soon deliver drugs and perform microsurgery.

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JSTO IN THE NEWS2

Scientists at the University of California–San Diego are speeding ahead to provide new protections for the warfighter by detecting and eliminating biothreats on the battlefield.

Principal investigator, Professor Joseph Wang, Dr. Wei Gao and their team, in a research project managed by Dr. Brian Pate of DTRA CB/JSTO, recently developed a micromotor-based approach for rapidly screening, capturing, isolating and destroying anthrax simulant spores with minimal sample preparation.

Micromotors are functionalized with the antibody B. globigii, a species of bacillus found in soil and decomposing organic matter, which recognizes, selectively captures and transports B. globigii spores in complex environmental matrices (e.g. pond scum). Research showed effective and efficient destruction of these anthrax simulant spores as evidenced via the micromotor-induced mixing of a mild oxidizing solution.

A significant benefit to the warfighter on the battlefield, this approach charts a new biodefense capability trajectory for micromotor based multifunctional systems that rapidly destroy biological threats.

The full journal article, “Micromotors to capture and destroy anthrax simulant spores,” can be found in the January 8, 2015, edition of Analyst.

Seek and Destroy: Micromotors Rapidly Eliminate Biothreats on the Battlefield

POC: Dr. Brian Pate, brian.pate@dtra.mil

Dengue Virus ... (continued from page 1)

POC: Dr. Brian Pate, brian.pate@dtra.mil

process. The scientists are developing protein-constrained membrane models to determine the first estimates of free energies in the fusion of virus to a human host endosomal membrane.

The virus is coated by an icosahedral shell consisting of 90 envelope protein dimers that convert to trimers when exposed to a low pH environment. These trimers then promote fusion of the DV membrane with the membrane of the host endosome. The viral fusion proteins bind strongly to the anionic lipids to

overcome the fusion barrier. The virus fusion peptides can then insert at the host membrane hydrophobic/head group interface, thus infecting the host.

By understanding the viral process mechanism, scientists will further develop protection for warfighter exposure to DV and other viruses. For further information, read “Molecular Basis of Endosomal-membrane Association for the Dengue Virus Envelope protein,” in Biochimica et Biophysica Acta – Biomembranes.

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Lead DoD science and technology to anticipate, defend, and safeguard against chemical and biological threats for the Warfighter and the Nation. JSTO IN THE NEWS 3

POC: Dr. Brian Pate, brian.pate@dtra.mil

Man-made Micromachines ... (continued from page 1)

due to the fact that the main degradation production of the present micromotors in Zn is an essential general nutrient involved in many aspects of metabolism and found in all body tissues.

These findings are significant in developing advanced medical countermeasures for our warfighters, as they, along with the absence of toxic effects in the stomach, suggest that the movement of micromotors provides distinct advantages for in vivo biomedical applications such as directed drug delivery, diagnostics, and nanosurgery.

Read more about this research in the ACS Nano Journal article “Artificial Micromotors in the Mouse’s Stomach: A Step toward in Vivo Use of Synthetic Motors.”

The Defense Threat

Reduction Agency’s (DTRA)

Research and Development

(J9) Directorate, Chemical

and Biological (CB)

Technologies Department,

serves as the Joint Science

and Technology Office for

Chemical and Biological

Defense. This publication

highlights the organization’s

accomplishments to protect

warfighters and citizens

through the innovative

application of science and

technology research.

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