In the last article, “Nanomedicine: A Vast Horizon from a Molecular Landscape-Part I, Introduction,” I briefly introduced the new and exciting field of “Nanomedicine” and reviewed the current funding support and areas of research and development. In this installment, I will first focus on representative companies and organizations and their researchers, and then close with a review of key interesting patents in this field.

Nanomedicine Companies

The state of Connecticut has committed significant resources in support of new innovation in bioscience and nanomedicine. Through Connecticut Innovations (“CI”), the state’s quasi-government investment fund, the state has two focused support programs: the Connecticut Bioscience Innovation Fund (“CBIF”) and the Regenerative Medicine Research Fund (“RMRF”), to facilitate the transition of bench-top innovation towards commercialization. Through CBIF, for example, the state is committed to investing $200 million over 10 years to support the research and development of local research institutes and entrepreneurs in bioscience. . These state initiatives continue to encourage the growth of nanomedicine companies.

Connecticut has several local companies playing a promising role in nanomedicine. IsoPlexis and New Haven Pharmaceuticals are both Yale spin-off startups. IsoPlexis is focusing on the development of microarray devices and technology for monitoring the immune response at the single cell level. New Haven Pharmaceuticals is developing a 24-hour release aspirin with novel capsules. Last year New Haven Pharmaceuticals received FDA approval for their DURLAZA™ (aspirin) for secondary prevention of stroke and acute cardiac events. Soft Tissue Regeneration, a UCONN spin-off, introduced a bio-resorbable scaffold for the reconstruction of the anterior cruciate ligament of the knee. Oxford Performance Materials, a pioneer in personalized medicine with approximately a 20-year history, is transferring their 3D printing technology to fabricate patient-specific polymeric implants. Beyond Connecticut, nanomedicine companies provide various products from concept-proofing to commercialization. Table 1 summarizes some of the representative companies in this field in Connecticut and beyond.

Table 1. Nanomedicine Companies
Company Name Location Highlights
Artificial Cell Technologies New Haven, CT Multilayer polypeptide nanofilm technology for creating micro/nanoparticles or capsules to make vaccines treating Respiratory Syncytial Virus and malaria
Biological Dynamics San Diego, CA TR(ACE)TM assay isolates and quantifies cell-free dsDNA directly from serum or plasma of cancer patients undergoing systemic therapies
BioRad Hercules, CA Droplet digital PCR, an integrated microfluidic system for high throughput PCR measurement
Circulomics Baltimore, MD Ligo-miR EZ, multiplexed microRNA profiling assay using microRNA ligation technique
Cytograft Tissue Engineering Novato, CA Tissue engineered blood vessels from autologous fibroblast sheets rolled into tubes
Dexcom San Diego, CA Dexcom G5TM, a miniature wearable continuous glucose monitoring system for diabetic patients
Emulate Boston, MA Organs-on-chip technology to create a new living system that emulates human biology for disease modeling and drug screening
Exicure Skokie, IL Nanomaterials for targeted drug delivery, especially for skin disease
Fluidigm Corporation South San Francisco, CA Microfluidic based single-cell DNA sequencing
Hepregen Medford, MA HepatoPac and HepatoMune, are engineered human microliver tissue for in vitro toxicity testing, drug screening, and disease modeling
Hesperos Orlando, FL Body-on-a-chip systems for toxicology testing
Humacyte Morrisville, NC Engineering “off-the-shelf” investigational human tissue replacement
HuREL Coproation North Brunswick, New Jersey “Liver-on-chip” for disease modeling and toxicity testing
Illumina San Diego, CA Microarray-based sequencing for genomic analysis
Ion Torrent Systems Guilford, CT Using semiconductor technology to deliver the fastest benchtop next gene sequencing
IsoPlexis Branford, CT Microarray devices for single-cell multiplex protein profiling targeting immunotherapeutics
LambdaVision Farmington, CT Novel materials for retinal implants
New Haven Pharmaceuticals New Haven, CT DURLAZA with Extend Release Capsules, to continuously release aspirin for 24 hours
Organovo San Diego, CA 3D Bioprinting for human tissues
Oxford Performance Materials South Windsor, CT 3D printed patient-specific polymeric implants
Soft Tissue Regeneration New Haven, CT L-C Ligament, a bioresorbable scaffold for the reconstruction of the anterior cruciate ligament of the knee
Woven Orthopedic Technologies Manchester, CT A novel woven materials for fastening screws in orthopedic implantation

Nanomedicine Research

Connecticut has an outstanding research record in nanomedicine. For example, Yale Biomedical Engineering has three major focus areas: drug delivery, tissue engineering, and imaging. Dr. W. Mark Saltzman was elected as a member of the National Academy of Medicine (NAM) for his contribution to developing novel nanomaterials for drug delivery. Dr. Laura Niklason is also a member of NAM, and is well-known for her research in vascular and lung tissue engineering. Dr. Themis Kyriakides, Dr. Tarek Fahmy, and Dr. Anjelica Gonzalez have multiple on-going research projects applying nanotechnology to tissue engineering, drug delivery and biomedical imaging. and developed unique microarray devices for highly multiplex protein measurements in single cells and genomic sequencing. There are also scientists in other departments contributing to nanomedicine, such as Dr. Donald Engelman, Dr. Peter Glazer, and Dr. Erik Shapiro. At the University of Connecticut Health Center (UCHC), Dr. Cato Laurencin has established an Institute for Regenerative Engineering, with Dr. Mei Wei, Dr. Sangamesh Kumbar, Dr. Syam Nukavarapu, and others to apply nanomaterials and nanotechnology to musculoskeletal regeneration and drug delivery. Also at UCONN Dr. Ki Chon is leading the Biomedical Engineering department with newly recruited members, such as Dr. Bin Feng, Dr. Kazunori Hoshino, and others to further strengthen the research of nanomedicine in diagnostics and therapeutics.

Outside of Connecticut, other outstanding researchers lead prominent research projects in different areas related to nanomedicine. Table 2 summarizes some representative key opinion leaders and their contribution in this field.

Table 2. Leaders in the research of nanomedicine
Research Scientist Research Institute Research Focus Company Affiliation (from Table 1)
W. Mark Saltzman Yale Bio-compatible polymeric materials for the controlled delivery of drugs, proteins, and genes, targeting at disease prevention and treatment; new materials for growth and assembly of tissues
Laura Niklason Yale Vascular and lung tissue engineering Humacyte
Themis Kyriakides Yale Nanomaterials and cell interaction, tissue engineering
Tarek Fahmy Yale Nanomaterials for drug delivery and biomedical imaging
Anjelica Gonzalez Yale Applying microtechnology to investigate the chemo-mechanics of immunobiological process
Rong Fan Yale Microchip platform for highly multiplexed protein measurement in single cells and for facilitating single cell genomic, epigenetic, and transcriptional profiling IsoPlexis
Donald Engelman Yale Synthetic nanomaterials for drug delivery
Peter Glazer Yale Nanomaterials for radiotherapy
Erik Shapiro Yale Nanomaterials as contrast agents for MRI
Cato Laurencin UCHC/UCONN Nanomaterials and nanotechnology for musculoskeletal tissue engineering Soft Tissue Regeneration
Wei Mei UCHC/UCONN Novel materials for bone tissue engineering
Sangamesh Kumbar UCHC/UCONN 3D polymer scaffold for bone repair and regeneration
Syam Nukavarapu UCHC/UCONN Composite materials for bone regeneration
Ki Chon UCONN Devices for monitoring and modulating physiological signals and wearable medical devices
Kazunori Hoshino UCONN Nano/micro-electromechanical system for cancer diagnostics, mechanical sensing, and optical imaging
Bin Feng UCONN Microdevices for neurosignal sensing and neuromulation
Robert Langer MIT Drug delivery, tissue engineering, and advanced biomaterials Artificial Cell Technologies
Donald Ingber Harvard University “Organs-on-chips” devices for disease modeling and drug screening, nanoparticles for therapeutics Good SIRS, Emulate
Sangeeta Bhatia MIT Micro/nanotechnologies to interface living and synthetic systems to improve cell therapies in liver diseases and the diagnosis and treatment of cancer Hepregen
Michael Schuler Cornell University “Body-on-a-chip”, a microsystem, to recapitulate the physiological environment in vitro, used for disease model and drug screening Hesperos
Dino Di Carlo UCLA Micro/nanofluidic technologies for recapitulating the physiological environment of biological system, developing diagnostics medical devices, and cellular engineering
Joseph DeSimone University of North Carolina 3D printing making medical devices and nanoparticles for cancer treatment Liquidia Technologies, Carbon3D
Chad Mirkin Northwestern University Nano-optical methods for synthesizing and fabricating novel materials with biological applications Exicure
Tza-Huei Wang Johns Hopkins University Developing and applying the technology of microfluidics, single molecule spectroscopy and functional nanoparticles, in biomarker-based diagnostics, prognostics and disease monitoring Circulomics

Nanomedicine Patents

Active research in nanomedicine has resulted in dynamic patent activity in this field. In diagnostics, microdevices have been developed to address challenges in clinical applications and nanomaterials have been utilized to explore novel biomarkers for disease diagnosis. U.S. Patent 9,188,586 discloses a microfluidics based methodology for high throughput multiplex protein profiling at single cell level. U.S. Patent 9,284,601 discloses microfluidic systems for high-throughput, droplet-based single molecule analyses. U.S. Patents 7,288,405, 8,647,861, and 8,865,464 describe in vitro organ-on-a-chip systems to mimic the physiological environment of human organs, targeting at disease modeling and drug screening. In therapeutics, nanotechnology has been widely used for targeted drug delivery. U.S. Patents 7,030,097, 7,534,448, 8,927,018, 9,248,121, and 9,139,827 described a wide variety of different nanomaterials, i.e., polymeric nanoparticles, metallic nanoparticles, porous materials, etc., for delivery of drugs or biomolecules such as, DNA, or RNA, to specific targets. U.S. Patents 8,252,517 and 8,465,775 described unique microtechnology based methods for making nanoparticles for drug delivery. In regenerative medicine, nanocomposite materials and 3D printed materials are used for selectively engineering tissues and organs.  U.S Patents 8,614,189 and 9,114,009 describe nanomaterials as scaffolds for tissue engineering. US. Patents 9,222,932 and 9,227,339 describe engineered organs made by 3D printing techniques. I will discuss more details and applications in diagnostics, therapeutics and regenerative medicine in following articles. Here, in Table 3 I summarize some of the representative patents mentioned herein.

Table 3. Patents Related to Nanomedicine
Patent Number Inventor(s) Assignee Title Issue Date
U.S. 9,188,586 Fan, et. al. Yale University System, device and method for high-throughput multi-plexed detection Nov. 17, 2015
U.S. 9,284,601 Wang, et. al. The Johns Hopkins University Microfluidic system for high-throughput, droplet-based single molecule analysis with low reagent consumption Mar. 15, 2016
U.S. 7,288,405 Schuler, et. al. Cornell Research Foundation Devices and methods for pharmacokinetic-based cell culture system Oct. 30, 2007
U.S. 8,647,861 Ingber, et. al. Children’s medical center corporation Organ mimic device with microchannels and methods of use and manufacturing thereof Feb. 11, 2014
U.S. 8,865,464 Takayama, et. al. The Regents of the Univerisity of Michigan Microfluidic cell culture device Oct. 21, 2014
U.S. 7,534,448 Saltzman, et. al. Yale University Methods of treatment with drug loaded polymeric materials May. 19, 2009
U.S. 7,030,097 Saltzman, et. al. Cornell Research Foundation Controlled nucleic acid delivery systems Apr. 18, 2006
U.S. 9,139,827 Mirkin, et. al. Northwestern University Polyvalent RNA-nanoparticle compositions Sep. 22, 2015
U.S. 9,248,121 Roorda Abbott Laboratories Medical devices for controlled drug release Feb. 2, 2016
U.S. 8,927,018 Laurencin, et. al. UCONN Immobilized metallic nanoparticles as unique materials for therapeutic and biosensor applications Jan. 6, 2015
U.S. 8,252,517 Thomas, et. al. MIT Stop flow interference lithography system Aug. 28, 2012
U.S. 8,465,775 DeSimone, et. al. The University of North Carolina at Chapel Hill Nanoparticle fabrication methods, systems, and materials for fabricating artificial red blood cells Jun. 18, 2013
U.S. 8,614,189 Laurencin, et. al. UCONN Carbon nanotube composite scaffolds for bone tissue engineering Dec. 24, 2013
U.S. 9,114,009 Dvir, et. al. Children’s medical center corporation & MIT Nanowired three dimensional tissue scaffolds Aug. 25, 2015
U.S. 9,222,932 Shepherd, et. al. Organovo Engineered liver tissues, arrays thereof, and methods of making the same Dec. 29, 2015
U.S. 9,227,339 Murhpy, et. al. Organovo Devices, systems, and methods for the fabrication of tissue Jan. 5, 2016

Closing

The funding support from both private foundations and federal agencies, and the resulting research activities in nanomedicine indicate that this field is growing on very fertile ground with great prospects to move further into commercialization and clinical applications. The rapid development in nanomedicine will ultimately improve the quality of human life and health care. In my next installment in this series, we will explore the the diagnostic applications of nanomedicine. Stay tuned for that .

– Jing Zhou, PhD and Anthony D. Sabatelli, PhD, JD

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