G. Magnetocapsule containing encapsulated mouse pancreatic islet cells. (Copyright Nature Medicine, 2007.)

The national media recently featured stories about the research of Johns Hopkins University and Institute of NanoBioTechnology affiliated faculty members Jeff Bulte and Dara Kraitchman and other colleagues. The news was based on a technical report in Nature Medicine explaining how magnetocapsules—tiny capsules about 350μm in diameter made from a matrix of seaweed extract and iron—could help prevent the rejection of insulin-cell (islet) transplants in diabetics.

The semi-permeable magnetocapsules have pores large enough to allow the insulin to pass through but small enough to prevent antibodies directed against β-cells from the pancreas from entering and attacking. Magnetic resonance imaging was used to track delivery and engraftment.
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INBT undergraduate summer internship poster session. Credit: INBT/JHU

Ten weeks of research may not be everyone’s idea of the best way to spend a summer. But the students who participated in the first undergraduate summer internship program sponsored by the Johns Hopkins University Institute for NanoBioTechnology will tell you it was a summer well spent.

INBT awarded a total of $35,000 to support the work of 10 students pursuing original projects in the labs of Johns Hopkins University and INBT affiliated faculty. The results of their findings were displayed during an Aug. 10 poster session at the Homewood campus. Posters were judged by INBT affiliated faculty and others who attended the gathering.

“It was a great experience spending time with the postdoctoral students and faculty members because during the school year I would not have had time to work with them so closely,“ says Fan Yang, who will be a senior in materials science this September.

Brady Sieber presenting his winning poster. Credit: INBT/JHU

Yang’s poster, “Pancreatic carcinoma imaging using fluorescent dye doped nanoparticles“ -research she completed with INBT faculty affiliates Professor Howard Katz (Materials Science and Engineering) and Professor Ellen Silbergeld (Environmental Health Sciences)—tied for best poster overall with Brady Sieber, this fall a senior in public health studies. Sieber worked with perflurocarbons to enhance the viability of encapsulated mesenchymal stem cells.

“It was exciting working with stem cells,“ Sieber says. “I learned that things like this take a little longer than you would think because there are always things along the way that you don’t expect to happen. You just have to keep trying new approaches, and hopefully you will get results that will be what you wanted.“ Sieber’s work was supervised by INBT affiliated faculty members Associate Professor Dara Kraitchman (Radiology) and Professor Jeff Bulte (Radiology).

Chih-Ping Mao, this fall a junior in biology, worked with INBT affiliated faculty member Assistant Professor Chien-Fu Hung (School of Medicine). Hung says, “The INBT interns were very talented; I was very happy to work with them,“ Hung says. “They learned very quickly, worked hard and participated in all aspects of research. I was quite impressed.“

In order to be considered for an internship, students were required to have experience in the development and use of advanced nano-materials and structures and techniques for nano-fabrication with an ultimate goal to solve important problems in biology, health and the environment and medicine. A review committee, made up of Hopkins faculty affiliated with INBT, received about 50 submissions from students in the Krieger School of Arts and Sciences, the Whiting School of Engineering, and the School of Medicine.

“The program was established to give undergraduates the opportunity to experience what it is like to conduct real scientific research,“ says Sue Porterfield, INBT administrative manager. “Next summer, we will be able to expand the program through funding from the National Science Foundation.“

Back left to right: Jaeyoon Chung, Jonathan Smits, Fan Yang, Brady Sieber. Front left to right: Anniruddha Ranjan, Joelle Sohn, Jeaho Park. Credit: INBT/JHU

Participants in this summer’s undergraduate nanobio research internship included:

Jaeyoon Chung
Research subject: “Rapid and highly sensitive analysis of c-reactive protein in human serum“
Advised by: Y.C. Lee (Biology), H.Q. Mao (Materials Science and Engineering)

Chih-Ping Mao
Research subject: “Polymeric nanoparticle-based gene delivery systems for the treatment of ovarian cancer“
Advised by: C.F. Hung (Pathology), Justin Hanes (Chemical & Biomolecular Engineering)

Jeaho Park
Research subject: “Magnetic quantum dots“
Advised by: Peter Searson (Materials Science and Engineering), Martin Pomper (Radiology)

Aniruddha Rajan
Research subject: “Nanoliter containers for on-demand remote release therapeutics“
Advised by: Robert Liddell (Radiology), David Gracias (Chemical & Biomolecular Engineering)

Brady Sieber
Research subject: “Using perfluorocarbons to enhance oxygen tension and improve cell viability of radiopaque encapsulated mesenchymal stem cells“
Advised by: Dara Kraitchman (Radiology), Jeff Bulte (Radiology)

Joelle Sohn
Research subject: “Regulation of cytoskeletal dynamics by Rho GTPases in ovarian cancer“
Advised by: Denis Wirtz (Chemical & Biomolecular Engineering)

Jonathan Smits
Research subject: “Synthesis and characterization of templated hetero-trimer collagen mimic peptide“
Advised by: Michael Yu (Materials Science and Engineering)

JHU enterprise chief, INBT director to speak at RMI event

Aris Melissaratos

Two Johns Hopkins University experts will discuss the potential impact of nanobiotechnology on the direction of regional manufacturing at an Aug. 23 gathering hosted by the Regional Manufacturing Institute of Maryland.

Aris Melissaratos, senior advisor to the president for enterprise development at Johns Hopkins and former secretary of the Maryland Department of Business and Economic Development, and Peter Searson, professor in the Whiting School of Engineering and director of the university’s Institute for NanoBioTechnology, will speak at “From Research to Practice: An Evening with Aris Melissaratos.”

The event is scheduled for Thursday, Aug. 23, from 5:30 p.m. to 7:30 p.m. at the Baltimore Museum of Industry, 1415 Key Highway, Baltimore, Md. 21230.

Melissaratos says entrepreneurial initiatives at Johns Hopkins, particularly those in the interdisciplinary realm of nanobiotechnology, will play a major role in driving the direction of manufacturing in the region.

Nanobiotechnology employs tools from both physical and life sciences to devise extremely small-scale approaches — devices and materials on the order of billionths of a meter in size — to health and environmental problems.

Peter Searson

“Dr. Searson is an exciting visionary in nanobiotechnology,” Melissaratos says. “The breakthroughs that will come in this area will direct the future of industry.”

RMI, a non-profit association, was created for manufacturers in the Baltimore metropolitan area and involves representatives of business, government, education, labor and the community.

“Our hope is that this evening will be an opportunity to bring together experts like Dr. Searson with those people involved in translating technology into a manufactured product,” says Michael Galiazzo, executive director of RMI. “The work conducted by the faculty affiliated with the INBT represents the future of manufacturing in Maryland.”

For more information on “From Research to Practice: An Evening with Aris Melissaratos” and to register online, visit http://www.marylandmanufacturing.info

Related Web site:
Peter Searson page: http://www.jhu.edu/~matsci/people/faculty/searson/searson.html

The American Association of Nanomedicine.

The 3rd annual meeting of the American Academy of Nanomedicine (AANM) —Sept. 7-9 at the University of California, San Diego (UCSD)—will provide a platform for those engaged in nanomedicine research to establish potential collaborations. Some of the keynote speakers and their topics include:

David Cheresh
Professor of pathology, Tumor Growth, Invasion, and Metastasis Program at the Moores Cancer Center UCSD Medical Center
“Nanoparticle-mediated targeted drug delivery to the tumor vasculature“

Peixuan Guo
Dane and Mary Louise Miller Endowed Chair in Biomedical Engineering
Director of NIH Nanomedicine Development Center
Cincinnati University College of Medicine
“Instrumentation and metrology for single molecule counting in nanoparticles by a customized single molecule dual-view“

Jean M.J. Fréchet
Professor of Chemistry and Chemical Engineering, Rapoport Chair of Organic Chemistry
University of California, Berkeley and Director of the Organic Nanostructures Facility, The Molecular Foundry, Lawrence Berkeley National Laboratory
“Dendrimers for the conjugation of small molecule drugs“

AANM is a professional, academic and medical society dedicated to advancing research in nanomedicine. Fore more information about AANM, meeting registration, or membership, go to http://www.aananomed.org/.

To learn more about nanomedicine visit our Q&A: The Nanomedicine Future, an interview conducted last year with Chairman of AANM Chiming Wei, MD, PhD, Associate Professor in the department of Surgery at Johns Hopkins University and an Institute for NanoBioTechnology faculty member.

The latest issue of Johns Hopkins University Engineering magazine features the article “Body Builders“ by Sara Achenbach. The article mentions the work of several Johns Hopkins University and Institute for NanoBioTechnology affiliated faculty members. Work highlighted includes that of Andreas Andreou (Electrical and Computer Engineering); Marc Ostermeier (Chemical and Biomolecular Engineering); Michael Yu (Materials Science and Engineering); Jennifer Elisseeff (Biomedical Engineering Institute); and Nitish Thakor (Biomedical Engineering).

Artificial Intelligence: Andreou’s team has developed a silicon cortex using nanoscale 3-D silicon on insulator complementary metal oxide semiconductor technology. By stacking super thin microchips in this nano-sized cortex, his groups has simulated more closely than before the natural circuitry of the brain.

Protein Switches: Ostermeier’s group is looking at the ways protein switches work to respond to complex signals. His work is funded by grants from National Institutes of Health, National Science Foundation and an INBT grant.

Tissue Scaffolds: Funded in part by a National Science Foundation CAREER Award, Yu is creating biomedical applications for modified collagen to prevent the formation of scar tissue and to prevent organ transplant rejection.

Hydrogel Scaffolds: Elisseeff uses hydrogel scaffolds to develop artificial adhesives for the eye to repair corneal damage and help close incisions following cataract surgery. Another Elisseef led team is investigating methods of creating artificial cartilage.

Robotic Hands: Thakor and colleagues are testing some brain-controlled robotic prosthetic hands with very human-like qualities. This work is funded by the Defense Advanced Research Projects Agency through the Johns Hopkins Applied Physics Lab.

To read the entire article from Johns Hopkins Engineering, visit: http://wse.jhu.edu/include/content/pdf/engmag-summer07/bodybuilders.pdf.

Though no one diagnosed with cystic fibrosis has ever been cured, new research by Justin Hanes and his colleagues offers a potential solution to one of the biggest obstacles impeding treatment of this devastating and chronic illness—getting past the mucus barrier.

“The gene that could cure cystic fibrosis has been known since 1989. However, the disease hasn’t been cured because no one knows how to deliver the curative gene to cells lining the airways of the lungs,“ says Hanes, associate professor in the Department of Chemical and Biomolecular Engineering and an executive committee member of the Institute for NanoBioTechnology. “A major change in the next decade will be an increased focus on delivery technologies.“

Mucus, that sticky and highly viscous substance that lines the lungs, eyes, the gastrointestinal tract, and female reproductive tract is proficient at blocking particles from penetrating the body. This is a good thing when those particles are bacteria or viruses but bad when they are vehicles for life-saving therapies.

Hanes and fellow researchers are finding ways to get drug-delivering particles past those sticky mucus linings. Most importantly, they’re discovering how to get higher density nanoparticles through mucus at a faster pace, thereby beating the body’s speedy attempts to flush its contaminated mucus away.

In a paper published in the January 2007 Proceedings of the National Academy of Sciences, Hanes’ team reported that a coating of polyethylene glycol (PEG) keeps particles from sticking to mucus. PEG had previously been reported as highly adhesive to mucus, but the team showed that PEG molecules with low enough molecular weight (i.e., smaller versions of the molecule) were not.

In one of the most surprising and important findings, the researchers, including first author Samuel K. Lai (PhD candidate in Chemical and Biomolecular Engineering), demonstrated that particles coated with PEG moved through human mucus almost as fast as they move through water; particles without the coating had previously been shown to be completely immobile in human mucus.

The team also reported that openings in the mucus mesh lining are much larger than previously thought. This, in turn, means that much larger particles than once believed possible have the potential to pass through the protective mucus barrier, Hanes says. Larger particles are desired for commercial products since they are easier to efficiently load with drugs and are capable of sustaining the release of drug molecules for longer periods of time.

“These findings set the stage for a new generation of nanomedicines that can be delivered directly to affected areas to treat a host of important diseases, such as lung, colon, and cervical cancer, asthma, COPD (chronic obstructive pulmonary disease), inflammatory bowel disease, cystic fibrosis, and more,“ says Hanes.

The preceding article was adapted from “Bypassing the mucus barrier: a “Slick“ Answer“ by Angela Roberts in Johns Hopkins Engineering: The Magazine of the Johns Hopkins Whiting School of Engineering, Summer 2007.

To read the full text of this article: Lai, S.K., O’Hanlon, D.E., Harrold, S., Man, S.T., Wang Y., Cone, R., Hanes, J. (Jan. 23, 2007). Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proceedings of the National Academy of Sciences 104, 1482-1487, please click here.

To read the abstract in PubMed, click here.

Read more: Coated Nanoparticles Solve Sticky Drug-Delivery Problem on Headlines at Hopkins

By Angela Roberts (published as Back to the Classroom at Alumni College*)

“Our goal,“ said Peter Searson, director of Johns Hopkins’ Institute for NanoBioTechnology (INBT), “is to establish Hopkins as the world leader in nanobiotechnology. Or, as I like to say, world domination.“ The 40 or so alumni gathered in Hodson Hall appreciated Searson’s humor, especially at the beginning of an intensive, hourlong lecture on the characteristics of the very tiny things the INBT faculty researches.

Searson, who helped launch the INBT in 2006, was one of two Whiting School professors who hosted Alumni College during the Johns Hopkins Homecoming and Reunion in April. He and civil engineering professor Tony Dalrymple, who spoke on “Natural Hazards: Lessons Learned from the Tsunami and the Hurricane,“ led independent sessions open to all alumni, during which they explained their research and the latest developments in their fields.

Mac McLeod ’57 and his wife, Lenore Danielson, who were visiting from their home in New Jersey, attended Searson’s morning lecture. “Professor Searson is one of the best lecturers I’ve heard,“ McLeod commented. “It’s a fascinating field and he’s a fascinating teacher. It makes you feel like you’d like to go back to school and be in his class. It leaves you with a lot to think about, and it’s amazing to learn that the cost of solving the problems they’re working on is so high.“ His wife interjected, “And to realize that the cost of not solving them is equally high.“

Searson’s presentation began with talk of size and scale. He explained that a “bucky ball“—a fundamental building component in the world of nanobiotechnology—is only a nanometer wide. By comparison, a single strand of a human hair is 100,000 nanometers wide. “We can make materials that are smaller than cells, which means that we can build things that can go into cells and deliver drugs,“ he noted. He went on to discuss how nanobiotechnology engineers and scientists are searching for new therapies, new diagnostic tools, and a better understanding of the relationship between cells and disease.

While alumni from ages 30 to 90 listened intently, Searson continued on to explain the logistics of shrinking things to the nano scale, such as the discovery that when something gets smaller, a higher percentage of its atoms are on the surface. The result? Everything from fibers for athletic clothing that “wick away“ liquid to drug delivery systems that target cancer cells.

Searson’s lecture ended with projections for what the future of nanobiotechnology holds in store for the world. “We will be able to take a ‘smart pill’ that will be programmed to report on its position and status in the body before releasing the correct dose of drugs,“ he predicted. Searson believes Johns Hopkins will be at the forefront of such discoveries, and he predicts we will see this technology hit the marketplace within decades.

*Originally published in Johns Hopkins Engineering: The Magazine of the Johns Hopkins Whiting School of Engineering, Summer 2007.

The Johns Hopkins University Institute for NanoBioTechnology will host a booth at the National Research Conference of the Historically Black Colleges & Universities Undergraduate Program (HBCU-UP) at the Grand Hyatt Hotel in Washington, DC, Oct. 4-7.
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