Hopkins Biomaterials Day Symposium Oct. 29

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Johns Hopkins Institute for NanoBioTechnology is a sponsor of the annual Biomaterials Day Symposium to be held Friday, Oct. 29 , from 8 a.m. to 5 p.m. in Charles Commons at the Homewood campus.

The goal of this of regional mini-symposium is to show-case all biomaterials related research happening at Johns Hopkins University, University of Maryland, and Pennsylvania State University, to stimulate further collaborations among peers, and to promote student participation in biomaterials research at all levels. Several keynote speakers will be giving talks on various aspects of biomaterials science, engineering and applications.

Join INBT, JHU and our neighboring research universities for this day-long event. You and your lab are invited to share your work on biomaterials at this symposium. Previously presented research may be presented here again. The registration is free and lunch is included.

Society for Biomaterials

Cells studied in 3-D may reveal novel cancer targets

Stephanie Fraley

Stephanie Fraley, a doctoral student in chemical and biomolecular engineering, was lead author of the study. Photo by Will Kirk/HomewoodPhoto.jhu.edu

Showing movies in 3-D has produced a box-office bonanza in recent months. Could viewing cell behavior in three dimensions lead to important advances in cancer research? A new study led by Johns Hopkins University engineers indicates it may happen. Looking at cells in 3-D, the team members concluded, yields more accurate information that could help develop drugs to prevent cancer’s spread.

“Finding out how cells move and stick to surfaces is critical to our understanding of cancer and other diseases. But most of what we know about these behaviors has been learned in the 2-D environment of Petri dishes,” said Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center and principal investigator of the study. “Our study demonstrates for the first time that the way cells move inside a three-dimensional environment, such as the human body, is fundamentally different from the behavior we’ve seen in conventional flat lab dishes. It’s both qualitatively and quantitatively different.”

One implication of this discovery is that the results produced by a common high-speed method of screening drugs to prevent cell migration on flat substrates are, at best, misleading, said Wirtz, who also is the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering at Johns Hopkins. This is important because cell movement is related to the spread of cancer, Wirtz said. “Our study identified possible targets to dramatically slow down cell invasion in a three-dimensional matrix.”

When cells are grown in two dimensions, Wirtz said, certain proteins help to form long-lived attachments called focal adhesions on surfaces. Under these 2-D conditions, these adhesions can last several seconds to several minutes. The cell also develops a broad, fan-shaped protrusion called a lamella along its leading edges, which helps move it forward. “In 3-D, the shape is completely different,” Wirtz said. “It is more spindlelike with two pointed protrusions at opposite ends. Focal adhesions, if they exist at all, are so tiny and so short-lived they cannot be resolved with microscopy.”

The study’s lead author, Stephanie Fraley, a Johns Hopkins doctoral student in Chemical and Biomolecular Engineering, said that the shape and mode of movement for cells in 2-D are merely an “artifact of their environment,” which could produce misleading results when testing the effect of different drugs. “It is much more difficult to do 3-D cell culture than it is to do 2-D cell culture,” Fraley said. “Typically, any kind of drug study that you do is conducted in 2D cell cultures before it is carried over into animal models. Sometimes, drug study results don’t resemble the outcomes of clinical studies. This may be one of the keys to understanding why things don’t always match up.”

collagen fibers

Reflection confocal micrograph of collagen fibers of a 3D matrix with cancer cells embedded. Image by Stephanie Fraley/Wirtz Lab

Fraley’s faculty supervisor, Wirtz, suggested that part of the reason for the disconnect could be that even in studies that are called 3-D, the top of the cells are still located above the matrix. “Most of the work has been for cells only partially embedded in a matrix, which we call 2.5-D,” he said. “Our paper shows the fundamental difference between 3-D and 2.5-D: Focal adhesions disappear, and the role of focal adhesion proteins in regulating cell motility becomes different.”

Wirtz added that “because loss of adhesion and enhanced cell movement are hallmarks of cancer,” his team’s findings should radically alter the way cells are cultured for drug studies. For example, the team found that in a 3-D environment, cells possessing the protein zyxin would move in a random way, exploring their local environment. But when the gene for zyxin was disabled, the cells traveled in a rapid and persistent, almost one-dimensional pathway far from their place of origin.

Fraley said such cells might even travel back down the same pathways they had already explored. “It turns out that zyxin is misregulated in many cancers,” Fraley said. Therefore, she added, an understanding of the function of proteins like zyxin in a 3-D cell culture is critical to understanding how cancer spreads, or metastasizes. “Of course tumor growth is important, but what kills most cancer patients is metastasis,” she said.

To study cells in 3-D, the team coated a glass slide with layers of collagen-enriched gel several millimeters thick. Collagen, the most abundant protein in the body, forms a network in the gel of cross-linked fibers similar to the natural extracellular matrix scaffold upon which cells grow in the body. The researchers then mixed cells into the gel before it set. Next, they used an inverted confocal microscope to view from below the cells traveling within the gel matrix. The displacement of tiny beads embedded in the gel was used to show movement of the collagen fibers as the cells extended protrusions in both directions and then pulled inward before releasing one fiber and propelling themselves forward.

Fraley compared the movement of the cells to a person trying to maneuver through an obstacle course crisscrossed with bungee cords. “Cells move by extending one protrusion forward and another backward, contracting inward, and then releasing one of the contacts before releasing the other,” she said. Ultimately, the cell moves in the direction of the contact released last.

When a cell moves along on a 2-D surface, the underside of the cell is in constant contact with a surface, where it can form many large and long-lasting focal adhesions. Cells moving in 3-D environments, however, only make brief contacts with the network of collagen fibers surrounding them–contacts too small to see and too short-lived to even measure, the researchers observed.

“We think the same focal adhesion proteins identified in 2-D situations play a role in 3-D motility, but their role in 3-D is completely different and unknown,” Wirtz said. “There is more we need to discover.”

Fraley said her future research will be focused specifically on the role of mechanosensory proteins like zyxin on motility, as well as how factors such as gel matrix pore size and stiffness affect cell migration in 3-D.

Co-investigators on this research from Washington University in St. Louis were Gregory D. Longmore, a professor of medicine, and his postdoctoral fellow Yunfeng Feng, both of whom are affiliated with the university’s BRIGHT Institute. Longmore and Wirtz lead one of three core projects that are the focus of the Johns Hopkins Engineering in Oncology Center, a National Cancer Institute-funded Physical Sciences in Oncology Center. Additional Johns Hopkins authors, all from the Department of Chemical and Biomolecular Engineering, were Alfredo Celedon, a recent doctoral recipient; Ranjini Krishnamurthy, a recent bachelor’s degree recipient; and Dong-Hwee Kim, a current doctoral student.

Funding for the research was provided by the National Cancer Institute.  This study, a collaboration with researchers at Washington University in St. Louis, appeared in the June issue of Nature Cell Biology.

Related links:

Johns Hopkins Engineering in Oncology Center

Department of Chemical and Biomolecular Engineering

Watch a related video on YouTube

Story by Mary Spiro

Lights! Camera! Science!

 

INBT Web Director Martin Rietveld works on protocol video with PhD student Yu-Ja Huang. (Photo:MSpiro)

Everything about movie making seems so glamorous. From beautiful stars to special effects, making films might appear magical. But actually, when you break it down, shooting a film is not unlike performing experiments in a lab. And, just as reading the script would be far less entertaining as seeing a film, reading a protocol might be confusing until the steps were performed in real life.

That’s the philosophy behind a new effort at Johns Hopkins Institute for NanoBioTechnology: produce short films describing recently published research and the protocols that go with them. The movies are produced collaboratively with INBT’s science writer Mary Spiro, INBT’s Animation Studio director Martin Rietveld, and the scientists and engineers involved.

The INBT Animation Studio already has several research-oriented films to its credit. The animation skills of Rietveld and his student crew have taken us inside a lipid bilayer and carried us along a fiber of collagen. INBT also has produced several video news releases using the talent of students in the annual science communication course.

Recently, however, INBT produced its first film describing a protocol from Nature Methods. Investigators Bridget Wildt, a PhD in materials science and engineering, Peter Searson, Reynolds Professor of Materials Science and Engineering, and Denis Wirtz, Smoot Professor of Chemical and Biomolecular Engineering, served as technical consultants for the production. The research was part of Johns Hopkins Engineering in Oncology Center, of which Wirtz is the director.

Materials science and engineering PhD candidate Yu-Ja Huang performs each step in assembling the Hopkins team’s device and demonstrates how to conduct programmed cell detachment experiments. “Studying cell detachment at the subcellular level is critical to understanding the way cancer cells metastasize,” Searson said. “Development of scientific methods to study cell detachment may guide us to prevent, limit or slow down the deadly spreading of cancer cells.”

Using a draft script developed by Wildt and Searson, Spiro simplified the text further for narrator, materials science and engineering PhD candidate Andrew Wong. Rietveld recorded Huang as he performed the protocol and refined the script further during filming. Viewing the final cut, Wong was able to read the script in a conversational and friendly tone.

You can watch the version of this new protocol video on INBT’s YouTube channel. The film may never earn an Academy Award, but we hope it will help specialists, and even the general public, to understand this unusual and complex procedure.

Related Links:

Check our INBT’s channel on YouTube.

Engineering in Oncology Center

Story by Mary Spiro

INBT welcomes 16 summer nanobio research interns

For 10 weeks this summer, 16 students from universities across the country will join the highly competitive Johns Hopkins Institute for Nanobiotechnology (INBT) Research Experience for Undergraduates (REU). The internship is funded by the National Science Foundation (NSF) and is supported and administered by INBT.

This is the third year of INBT’s REU program, and this group represents the institute’s largest group. Students are being mentored by faculty, graduate students and postdoctoral fellows in INBT affiliated laboratories across Hopkins. At the end of the 10-week research program, they will present their findings at a university-wide collaborative research poster session held with other summer interns from across several divisions.

In November 2009, NSF reported that over the last decade 10 times more white students will have earned doctoral degrees in science and engineering disciplines than minority students. Acknowledging this fact yet resolving not to accept it as status quo, INBT has employed aggressive measures to increase the number of individuals from underrepresented groups who apply to its educational programs.

“The nanobiotechnology REU has been one of the most successful and popular programs for INBT,” says Ashanti Edwards, senior education program coordinator for the institute. “The program has consistently attracted the best and the brightest students interested in research from top universities across the nation. The REU program was launched as a conduit to attract highly talented and motivated research students to pursue academic careers in research, particularly women and minority scholars. The program is highly competitive. For summer 2010, the number of applicants for the 10 slots in the program rose to nearly 500, twice what it had been the year before.”

Johns Hopkins Institute for NanoBioTechnology Summer REU Students. (Photos by Mary Spiro)

INBT’s summer 2010 REU students include pictured from top to bottom, from left to right:

Top row

Joshua Austin, computer science and math major from UMBC, is working with Jeff Gray, associate professor of chemical and biomolecular engineering, Whiting School of Engineering.

Mary Bedard, biochemistry and Spanish major from Elon University, is working with J.D. Tovar, assistant professor of chemistry, Krieger School of Arts and Sciences.

Kameron Black, neuroscience major from the University of California, Riverside, is working in the lab of Ted Dawson, professor of neuroscience, School of Medicine

Obafemi Ifelowo, who majors in molecular biology, biochemistry and bioinformatics at Towson University, is working with Jordan Green, assistant professor of biomedical engineering, School of Medicine.

Second row

Alfred Irungu, mechanical engineering major at UMBC, is working with German Drazer, assistant professor of chemical and biomolecular engineering, Whiting School of Engineering.

Ceslee Montgomery, human biology major from Stanford University, is working in the lab of Doug Robinson, associate professor of cell biology, School of Medicine.

Makeda Moore, biology major from Alabama A & M University, is working with Sharon Gerecht, assistant professor of chemical and biomolecular Engineering, Whiting School of Engineering.

Christopher Ojeda, biomedical engineering major from New Jersey Institute of Technology, is working in the lab of Michael Yu, assistant professor of Materials Science and Engineering, Whiting School of Engineering.

Third row

Katrin Passlack, mechanical engineering and kinesiology major at the University of Oklahoma, is working with Jeff Wang, associate professor of mechanical engineering, Whiting School of Engineering.

Roberto Rivera, chemical engineering major from the University of Puerto Rico, Mayaguez, is working in the lab of Nina Markovic, associate professor of physics, Krieger School of Arts and Sciences.

D. Kyle Robinson, bioengineering major from Oregon State University, is working in the lab of Denis Wirtz, professor of chemical and biomolecular engineering, Whiting School of Engineering. In addition, Kyle is the first REU intern for Johns Hopkins new Engineering in Oncology Center, of which Wirtz is director.

Russell Salamo, biology major from the University of Arkansas, is working with Kalina Hristova, associate professor of materials science and engineering, Whiting School of Engineering.

Bottom row

Quinton Smith, major in chemical engineering with a bioengineering concentration from the University of New Mexico, is working with Sharon Gerecht, assistant professor of chemical and biomolecular engineering, Whiting School of Engineering.

David To, chemistry major from Wittenberg University, is working with assistant professor Hai-Quan Mao in the department of materials science and engineering, Whiting School of Engineering.

Alan Winter, biology systems engineering major from Kansas State University, is working with Professor Peter Searson in the department of materials science and engineering, Whiting School of Engineering. Searson is the director of INBT.

Mary Zuniga, biology major a Northern Arizona University, is working in the lab of David Gracias, associate professor of chemical and biomolecular engineering, Whiting School of Engineering.

Related Links:

Johns Hopkins NanoBio Research Experience for Undergraduates

NanoBio Magazine premieres at INBT annual symposium

INBT launches new annual magazine.

As attendees arrived at the Johns Hopkins School of Public Health for the Institute for NanoBioTechnology’s (INBT) fourth annual symposium on April 29, they received the first edition of NanoBio Magazine. The new 32-page publication, which served as both the symposium program and as an attractive way to highlight some of INBT’s research in a more comprehensive way, will be published annually.

NanoBio Magazine, produced under the direction of INBT science writer Mary Spiro and INBT web director Martin Rietveld, showcases articles and photography about the institutes’s research, educational, corporate partnership and outreach programs. Articles were written by INBT staff, as well as students from the science communications course taught by Spiro each January during intersession. Photography came  from students who have participated in INBT supported educational programs, INBT staff, and from affiliated faculty members. The graphic design was created by Y.L. Media, LLC. of Baltimore.

“The magazine represents, in a creative and artistic way, the highly interdisciplinary spirit that is a fundamental mission of INBT,” Spiro said. “It was truly a collaborative effort that pulled content from our affiliated faculty and students  in every division and at every academic level that INBT serves. I hope people will learn what INBT is all about by reading it.”

Printed copies of NanoBio Magazine are available upon request by contacting Mary Spiro at mspiro@jhu.edu. Or, download a PDF version of NanoBio Magazine here:  nanobio-magazine_fordownload

Andrew Wong and Noah Tremblay peruse the first issue of NanoBio Magazine. (Photo by Charli Dvoracek/INBT)

Poster presenters needed for symposium on environmental, health impacts of nanotech

2009 INBT Poster Session (Photo: Jon Christofersen)

Poster titles are now being accepted for Johns Hopkins Institute for NanoBioTechnology’s fourth annual symposium, “Environmental and Health Impacts of Engineered Nanomaterials” set for Thursday, April 29, at the Bloomberg School of Public Health. Researchers from across the university, from government and industry, and from other universities are invited to submit posters by the deadline of April 22.

All students, faculty and staff affiliated with any Johns Hopkins campus or school may attend the symposium for free. Students from UMBC and Morgan State University may also attend at no cost.

This year’s symposium brings together faculty experts engaged in various aspects of nanotechnology risk assessment and management research. Jonathan Links, an INBT-affiliated professor in the Department of Environmental Health Sciences at the Bloomberg School, assembled the slate of speakers from across four divisions of the university.

Links said that this diversity reflects the multidisciplinary approach needed to effectively address questions of how nanomaterials move through and interact with the environment, and how they may impact biological organisms, including humans. Links added that despite some concerted efforts to assess risk, many questions remain unanswered about how engineered nanomaterials and nanoparticles impact human health and the environment.

“Without these data, we are flying blind. But when risk assessment is performed in tandem with research into beneficial applications, it helps researchers make better decisions about how nanotechnology is used in the future,” Links said.

Along with Links, professors from the Bloomberg School presenting talks at the symposium include Ellen Silbergeld, of Environmental Health Sciences, and Patrick Breysse, of Environmental Health Engineering and Environmental Health Sciences. William P. Ball, a professor in the Whiting School of Engineering’s Department of Geography and Environmental Engineering; Justin Hanes, a professor in the School of Medicine’s Department of Ophthalmology, with joint appointments in the Whiting School’s Department of Chemical and Biomolecular Engineering and the Bloomberg School’s Department of Environmental Health Sciences; and Howard Fairbrother, a professor in the Krieger School of Arts and Sciences’ Department of Chemistry, will talk about the transport of nanomaterials through environmental and biological systems, as well as the unusual properties of manufactured nanomaterials.

Tomas Guilarte, recently appointed chair of the Department of Environmental Health Sciences at Columbia University’s Mailman School of Public Health and a former professor at the Bloomberg School, will provide a presentation on neurotoxicity of nanoparticles. Ronald White, an associate scientist and deputy director of the Bloomberg School’s Risk Sciences and Public Policy Institute, will discuss policy implications based on risk assessment.

Symposium talks will be from 8:30 a.m. until noon in Sheldon Hall (W1214), and a poster session, with prizes for top presenters, will be held from 1:30 to 3 p.m. in Feinstone Hall (E2030).

To register for the symposium or to display a poster, click here.

For more information about INBT’s fourth annual symposium, click here.

Story by Mary Spiro

Probing the Soft Side with Nanoindentation Techniques

Michelle Oyen

Michelle L. Oyen of Cambridge University Engineering Department  will present the talk  ”Probing the Soft Side with Nanoindentation Techniques” on Wednesday, March 24 at 3 p.m. in Maryland Hall 110. Dr. Oyen is a lecturer in Mechanics of Biological Materials in the Mechanics and Materials Division and the Engineering for the Life Sciences group at Cambridge University. This seminar is hosted by Professor Tim Weihs and the Johns Hopkins University Department of Materials Science and Engineering. The talk is free and open to all Johns Hopkins faculty, staff and students.

Abstract

The mechanical properties of many “soft” materials are of interest for biomedical applications, including both natural tissues and hydrogels for tissue engineering applications. In the last 15 years, nanoindentation techniques have gained prominence in the mechanical testing community for three reasons: first, the fine resolution in load and displacement transducers, second the fine spatial resolution for mapping local mechanical properties, and finally the relative ease of performing mechanical testing. In the current studies, we extend the scope of nanoindentation testing with commercial indenters to quantitative measurements on kPa materials. Different forms of the material constitutive response were considered with an emphasis on time-dependent viscoelastic or poroelastic deformation. Applications are the considered for hydrated tissues and hydrogels including articular cartilage, bone and mechanically graded hydrogels. Further investigations using adaptations of these nanoindentation techniques examine nano-scale adhesion and mechanical outcomes in stem cell differentiation. This study demonstrates the potential for high-throughput mechanical screening of soft materials and for mapping property gradients in inhomogeneous materials as these approaches can now be extended to materials in the kilopascal elastic modulus range.

Environmental, health impacts of engineered nanomaterials theme of INBT’s annual symposium

By 2015, the National Science Foundation reports that the nanotechnology industry could be worth as much as $1 trillion. Nanomaterials have many beneficial applications for industry, medicine and basic scientific research. However, because nanomaterials are just a few atoms in size, they also may pose potential risks for human health and the environment.

Cross-sectional autoradiograms of rodent brains showing (A) control physiological state; and (B) and (C) showing distribution of brain injury from an injected neurotoxicant. Red areas indicate the highest concentrations of a biomarker that identifies brain areas that are damaged by the neurotoxicant. (Guilarte Lab/JHU)

Cross-sectional autoradiograms of rodent brains showing (A) control physiological state; and (B) and (C) showing distribution of brain injury from an injected neurotoxicant. Red areas indicate the highest concentrations of a biomarker that identifies brain areas that are damaged by the neurotoxicant. (Guilarte Lab/JHU)

To increase awareness of Hopkins’ research in this emerging area of investigation, the theme for the fourth annual symposium hosted by Johns Hopkins Institute for NanoBioTechnology (INBT) will be environmental and health impacts of engineered nanomaterials. INBT’s symposium will be held Thursday, April 29, from 8 a.m. to 3 p.m. at the university’s Bloomberg School of Public Health in Baltimore, Md.

Morning talks in Sheldon Hall by eight Hopkins faculty experts will discuss neurotoxicity, exposure assessment, manufacture and characterization of nanomaterials, policy implications and many other topics. In the afternoon, a poster session will be held in Feinstone Hall featuring nanobiotechnology research from across the university’s divisions.

INBT is seeking corporate sponsorships for the symposium. Interested parties should contact Thomas Fekete, INBT’s director of corporate partnerships at tmfeke@jhu.edu or 410-516-8891.

Media inquiries should be directed to Mary Spiro, INBT’s science writer and media relations director, at mspiro@jhu.edu or 410-516-4802.

A call for posters announcement will be made at a later date.

More:

Biodegradable nanoparticles ideal carrier for drug delivery

Johns Hopkins University researchers have created biodegradable nanosized particles that can easily slip through the body’s sticky and viscous mucus secretions to deliver a sustained-release medication cargo. The researchers say that these nanoparticles, which degrade over time into harmless components, could one day carry life-saving drugs to patients suffering from dozens of health conditions, including diseases of the eye, lung, gut or female reproductive tract.

The mucus-penetrating biodegradable nanoparticles were developed by an interdisciplinary team led by Justin Hanes, a professor of chemical and biomolecular engineering in Johns Hopkins’ Whiting School of Engineering*. The team’s work was reported recently in the Proceedings of the National Academy of Sciences. Hanes’ collaborators included cystic fibrosis expert Pamela Zeitlin, a professor of pediatrics at the Johns Hopkins School of Medicine and director of Pediatric Pulmonary Medicine at Johns Hopkins Children’s Center.

Individual biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University (shown here at microscale for easier imaging) displaying polymer coating as a red fluorescent glow. Hanes' biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. (Photo by Jie Fu/JHU)

Individual biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University (shown here at microscale for easier imaging) displaying polymer coating as a red fluorescent glow. Hanes’ biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. (Photo by Jie Fu/JHU)

These nanoparticles, Zeitlin said, could be an ideal means of delivering drugs to people with cystic fibrosis, a disease that kills children and adults by altering the mucus barriers in the lung and gut. “Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” she said. “In our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery. This work is critically important to moving forward with the next generation of small molecule– and gene-based therapies.”

Beyond their potential applications for cystic fibrosis patients, the nanoparticles also could be used to help treat disorders such as lung and cervical cancer and inflammation of the sinuses, eyes, lungs and gastrointestinal tract, said Benjamin C. Tang, lead author of the journal article and a postdoctoral fellow in the Department of Chemical and Biomolecular Engineering. “Chemotherapy is typically given to the whole body and has many undesired side effects,” he said. “If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively and improved outcomes may be achieved, especially for patients diagnosed with early stage non–small cell lung cancer.”

“If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively and improved outcomes may be achieved, especially for patients diagnosed with early stage non–small cell lung cancer.” ~ Ben Tang

In the lungs, eyes, gastrointestinal tract and other areas, the human body produces layers of mucus to protect sensitive tissue. But an undesirable side effect is that these mucus barriers can also keep helpful medications away.

In proof-of-concept experiments, previous research teams led by Hanes earlier demonstrated that latex particles coated with polyethylene glycol could slip past mucus coatings. But latex particles are not a practical material for delivering medication to human patients because they are not broken down by the body. In the new study, the researchers described how they took an important step forward in making new particles that biodegrade into harmless components while delivering their drug payload over time.

“The major advance here is that we were able to make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids,” Hanes said. “Previously, we could not get these kinds of sustained-release treatments through the body’s sticky mucus layers effectively.”

The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. An inner core, composed largely of polysebacic acid, or PSA, traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol, or PEG, molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.

In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally occurring molecules that are broken down and flushed away by the body through the kidney, for example. As the particles break down, the drugs loaded inside are released.

This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues.

Biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University visualized under a scanning electron microscope. (Photo by Ben Tang and Mark Koontz/JHU)

Biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University visualized under a scanning electron microscope. (Photo by Ben Tang and Mark Koontz/JHU)

Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”

PEG acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.

Hanes, Zeitlin, Lai and Fu are all affiliated with the Johns Hopkins Institute for NanoBioTechnology. Other authors on the paper are Ying-Ying Wang, Jung Soo Suk and Ming Yang, doctoral students in the Johns Hopkins Department of Biomedical Engineering; Michael P. Boyle, an associate professor in Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine; and Michelle Dawson, an assistant professor at the Georgia Institute of Technology.

This work was supported in part by funding from the National Institutes of Health, a National Center for Research Resources Clinical and Translational Science Award, the Cystic Fibrosis Foundation, the National Science Foundation and a Croucher Foundation Fellowship.

The technology described in the journal article is protected by patents managed by the Johns Hopkins Technology Transfer Office and is licensed exclusively by Kala Pharmaceuticals. Justin Hanes is a paid consultant to Kala Pharmaceuticals, a startup company in which he holds equity, and is a member of its board. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

(*At the time that this research was published, Hanes had his primary affiliation with the Whiting School of Engineering Department of Chemical and Biomolecular Engineering. Hanes’ current primary affiliation is with the Johns Hopkins School of Medicine Department of Ophthalmology.)

Related Links

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. PNAS 2009 106:19268-19273; published online before print November 9, 2009.  [Institutional access required.]

Hanes Lab

Johns Hopkins Children’s Center

Institute for NanoBioTechnology

Story by Mary Spiro and Jacob Koskimaki with materials provided by Johns Hopkins Technology Transfer.

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INBT, EOC directors named AAAS 2009 Fellows

The Johns Hopkins Whiting School of Engineering faculty members who direct the Institute for NanoBioTechnology and Engineering in Oncology Center both have been awarded the distinction of AAAS Fellow. Election as a Fellow is an honor bestowed upon AAAS members by their peers.

Peter Searson, INBT director. Photo by Will Kirk/JHU

Peter Searson, INBT director. Photo by Will Kirk/JHU

Denis Wirtz, EOC director. Photo by Will Kirk/JHU

Denis Wirtz, EOC director. Photo by Will Kirk/JHU

Peter C. Searson, the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering, was named for distinguished contributions to the field of surface chemistry and nanoscience. His research interests include surface and molecular engineering, and semiconductor quantum dots.

Searson directs the interdivisional Institute for NanoBioTechnology launched in May 2006, which brings together researchers from medicine, engineering, the sciences, and public health to create new knowledge and develop new technologies to revolutionize health care and medicine. INBT currently has more than 190 affiliated faculty members. Searson has secondary appointments in the Krieger School of Arts and Sciences Department of Physics and Astronomy and the Johns Hopkins School of Medicine Department of Oncology.

Denis Wirtz, the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering, was elected for his contributions to cell micromechanics and cell adhesion. He also was distinguished for his development and application for particle tracking methods to probe the micromechanical properties of living cells in normal conditions and disease state. Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression.

Wirtz directs the newly formed Johns Hopkins Engineering in Oncology Center. The EOC is a Physical Sciences in Oncology program center of the National Cancer Institute launched in October 2009 with a $14.8 million grant from the National Institutes of Health. EOC brings together experts in cancer biology, molecular and cellular biophysics, applied mathematics, materials science, and physics to study and model cellular mobility and the assorted biophysical forces involved in the spread of cancer. Wirtz also serves as co-director of the Institute for NanoBioTechnology and has a joint appointment in the Johns Hopkins School of Medicine Department of Oncology.

A total of seven Johns Hopkins faculty members were elected to AAAS this year. Read about all of them in a Johns Hopkins University press release listed in the links below.

This year 531 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications. New Fellows will be presented with an official certificate and a gold and blue (representing science and engineering, respectively) rosette pin on Feb. 20 at the AAAS Fellows Forum during the 2010 AAAS Annual Meeting in San Diego.  AAAS Fellows were announced in the AAAS News & Notes section of the journal Science on Dec. 18,  2009.

Story by Mary Spiro with materials provided by AAAS.

Seven Johns Hopkins Researchers Named 2009 AAAS Fellows

Searson Group Lab page

Wirtz Group Lab page

Johns Hopkins Institute for NanoBioTechnology

Whiting School of Engineering