MNIMBS works on development of therapeutics with a particle size small enough to overcome the barriers to deliver drugs, genetic materials and vaccines. The key here is that the small size of nanomaterials provides unique functional capabilities in biological systems. For example, in drug delivery the size of the endotheleal matrix or pores in the blood vessels limits their permealibility to sizes of less than 50nM. Similarly, the interstitial matrix or the space in between cells that nanoparticles have to find their way through to reach cells limits their permeability to less than 60 nM. We develop therapeutic materials that are small enough to overcome these barriers to delivery. Similar issues are involved in the mucosal epithelial penetration of vaccines and therapeutics, as well as in imaging agents and biological reporter systems.
Graphic by Paul D. Trombley
Our work is focused on several different technologies. Our first technology is a nanoemulsion that we originally developed as microbicidal agents. We currently further develop nanoemulsions as a unique type of adjuvant for nasopharyngeal vaccines for Influenza, Hepatitis B, RSV, etc. We have extended the nanoemulsion technology to include development of a novel, safe and rapidly effective treatment for war wounds and burns based on nanoemulsion (NE) formulations that have anti-microbial activity against a broad range of pathogens including antibiotic resistant strains.
We also design and synthesize multifunctional therapeutic nanodevices using dendritic polymers for the development of targeted chemotherapeutic treatments for cancer as well as research on treatment of macrophages ranging from arthritis to cardiovascular applications. We currently work on the synthesis of dendrimer-based morphine (analgesic) and naloxone (anti-analgesic) prodrugs utilizing ester and hypoxia-sensitive indolequinone linkers, respectively. Because of our linker choice, the active form of morphine should be continuously released from its prodrug when administered to a soldier, while the active form of naloxone should only be released when the soldier enters respiratory depression following a morphine overdose.
This work is further supported by studies of the transport mechanism and biological impact of non-viral vector polymers and polymer/DNA polyplexes, the characterization of the nanoscale poration of the plasma membrane by non-viral vectors and polyplexes and the structure of polymer/DNA polyplexes.
To advance these studies we have developed numerous devices, such as a photonic crystal biosensor for which we have obtained extremely high sensitivity with the ability to detect molecules as small as 250 Da (D-Biotin) with very high signal-to-noise ratio (1000), indicating room for further development in both small molecule detection and low-affinity binding measurements. Based on this success, a new company, PhotonAffinity LLC, has been formed by the MNIMBS principals in this project. The second area has been the first use of multiphoton spectroscopy to detect eosinophils. Please refer to our Annual Reports for descriptions of the various projects.
Accordingly, the success of MNIMBS’ progress is due to the interdisciplinary skills provided by a team of researchers with a wide range of expertise drawn from across campus in optics, chemistry, biology, applied physics, and computation. The interaction of nanoscale analytical science, synthetic materials science, and engineering with biological systems provides great opportunities for the biomedical sciences. Through our collaborative research projects we co-mentor students to give the students a truly multidisciplinary experience.
We formalized our educational mission by starting the Rackham Certificate in NanoBiology program. We are into our third year of NanoBiology Certificate program. To further grow the program, we work on outreach to students in the School of Engineering. Professors Orr and Baker each gave a talk to the students of the Nanotechnology and Integrated Microsystems Student Association. We bring together all MNIMBS member monthly for a working lunch during which one or two speakers present their work. This way we inform MNIMBS members of work that is ongoing and foster possible further collaborations. We also offer the broader University community Doan Lectures on nanotechnology topics as well as a Symposium approximately every year to 1.5 year. See listing of Events Hosted by MNIMBS.
We worked on infrastructure improvements. Early on we recognized the necessity of appropriate research space for our multidisciplinary activities. We created a clean room. We came to an agreement with the Department of Chemistry and the College of Literature, Science and the Arts to lease space. We invested in infrastructure improvements. We moved part of our operations to the Biomedical Sciences Research Building where there is opportunity to do some chemistry in an environment otherwise primarily intended for biological research. This building serves as a central hub for our students’ research and meeting activities. We also recognized the need for integrating science, medicine and informatics and established working relationships with the Center for Computational Medicine and Bioinformatics. We also invest regularly in cutting-edge research equipment to accelerate discovery. In addition, we make good use of the many Core facilities the University has to offer.
Although co-location has its challenges, we bridge these with frequent meetings, a good computing environment with resources to share and exchange data such as file servers and collaborative tools for work groups. While given opportunity to move our operations to North Campus, we have opted to stay centrally located nearest to our largest student population.
Thus far, the MNIMBS has successfully spun off two Ann Arbor based companies, NanoBio Corporation and PhotoAffinity, LLC. A third company, Avidimer Therapeutics, Inc., was started to commercialize the dendrimer-based technology. This company was closed during the economic down turn. Attempts are being made to restart this effort. Please refer to the Translational Research sections in the Annual Reports for descriptions of each company.
History of MNIMBS
In 1998, we formed the Center for Biologic Nanotechnology at the University of Michigan. At its core, the Center was formed to take advantage of the advances in the basic sciences and engineering and apply them to biological systems for medical applications. Participants came with an extremely wide range of expertise: optics, chemistry, biology, applied physics, and computation. The Center has successfully competed for nanomedicine research funding from a variety of sources, including the NIH Unconventional Innovations Program and NASA.
Over this period, the interdisciplinary collaboration has proven very successful. A tremendous amount of knowledge has been generated and, equally important, a large range of technology has been developed. Examples of nanomedicine applications include examination of nanoparticle interactions with membranes, synthesis and characterization of novel nanoparticles for targeted cancer treatment and MRI contrast enhancement, and development of minimally invasive two-photon fiber optic probes for detection and diagnosis of cancer. In each of these cases, the success of our investigation required the interdisciplinary skills provided by a team of researchers drawn from across campus.
A rate-limiting step was to facilitate productive interaction on nanobiology of these diverse scientific disciplines. To both recognize the success of the Center and improve the interaction of our multidisciplinary team of chemists, physicists, engineers and biologists collaborating on nanoscience in biology and medicine, the university expanded the Center into the "Michigan Nanotechnology Institute for Medicine and Biological Sciences" (MNIMBS) on April 21, 2005. James R. Baker Jr., M.D., the Ruth Dow Doan Professor of Biologic Nanotechnology and Chief of the Division of Allergy, serves as the Institute's first director. This Regentially chartered research institute brings together a larger group of interdisciplinary researchers to apply the techniques and knowledge from the physical sciences to biological and medical research. MNIMBS has centralized facilities and core resources that enable interdisciplinary teams of faculty to collaborate in nanomedicine and create a nanobiology graduate program. The interaction of nanoscale analytical science, synthetic materials science, and engineering with biological systems provides great opportunities for the biomedical sciences.
Accordingly, MNIMBS has direct Faculty and Staff employees as well as Faculty collaborators on grants and faculty members with varying levels of activity within MNIMBS, mentors and/or co-mentors of MNIMBS associated students, etc. For practical reasons, the MNIMBS Org Chart only includes direct MNIMBS employees and Faculty who directly collaborate on projects and may be Co-Investigator or Principal Investor on MNIMBS associated projects. Please refer to the listing of MNIMBS Mentors and Members and their expertise, which is followed by a listing of Direct MNIMBS Faculty, Staff, temporary staff, volunteers, Fellows, graduate students, undergraduate students, including UROP students.