A Trojan horse for tumors
With their flowing, tentacle-like arms, Associate Professor Shaoqin (Sarah) Gong’s polymer nanoparticles can locate, infiltrate and annihilate cancerous tumors — currently, in mice. Someday, tiny drug-delivery tools could be an alternative to chemotherapy as a targeted method for cancer drug delivery.
Because it often grows quickly, tumor tissue is “sloppy” tissue, with leaky vasculature. “Nanoparticles are unique for treating cancer because they can penetrate preferentially to tumor tissue,” says Gong.
While researchers form most nanoparticles via a dynamic process called self-assembly, many factors within the body — including polymer concentration, pH value, temperature, flow stress, and interaction with blood components, among others — can affect such nanoparticles’ in vivo stability. Gong and her colleagues focus on developing nanoparticles that provide excellent in vivo stability, pH-controlled drug release, and active tumor-targeting ability.
One of the nanoparticles they designed is called a unimolecular micelle, which is formed by individual, multi-armed (star-shaped) amphiphilic (both water-loving and water-averse) block copolymers. Since each nanoparticle is formed by one copolymer molecule that contains only covalent bonds, which are strong bonds, it exhibits excellent in vivo stability, says Gong. “The cancer-fighting drug is attached to the amphiphilic copolymer arms via pH-sensitive bonds,” she says. “In the bloodstream, when the pH is 7.4, it’s very stable, thus preventing premature drug release. However, once internalized by the tumor cells, the drug releases quickly because the pH-sensitive drug-polymer linkage breaks in the more acidic tumor cell environment.”
Gong’s team also attaches various ligands to the ends of certain arms. These ligands can recognize and bind to receptors either unique to, or overexpressed by, the tumor cells. This greatly enhances their cellular uptake and offers greater tumor cell death.
In addition to their potential for cancer therapy, the nanoparticles also can play a role in cancer diagnosis, a joint endeavor known as cancer theranostics. For this part of the research, Gong and her collaborators — Radiology Assistant Professor Weibo Cai (also BME), Medical Physics Visiting Assistant Professor Ian Rowland, and UW-Milwaukee Immunology Associate Professor Douglas Steeber — couple isotope-tagged multifunctional drug nanocarriers with magnetic resonance imaging and positron emission tomography scans that enable them to track nanoparticles in the body, identify tumor locations, and monitor therapeutic efficacy.
To perform microwave ablation, radiologists use ultrasound imaging or computed tomography to guide a thin antenna into the body. The antenna radiates enough energy to “cook” and kill cancerous cells.
Microwave ablation is akin to spot-treating cancer. With technological improvements, the procedure is well-suited for focal, or self-contained, tumors in such regions of the body as the liver, kidney or lungs, says Assistant Professor Chris Brace (also medical physics and radiology). “People are starting to think, ‘If new technologies can provide power and control, ablation could become a primary treatment option,’” he says.
As a UW-Madison electrical and computer engineering PhD student, Brace and biomedical engineering PhD student Paul Laeseke (now a radiology resident at Stanford University) studied microwave ablation under Electrical and Computer Engineering Professor Dan van der Weide and Robert Turrel Professor of Medical Imaging Fred Lee (both also BME). They addressed ways to deliver higher powers through small-diameter antennas that are safe for percutaneous use.
Hoping to capitalize on their advances, van der Weide, Lee and Susan Andrews-Winter founded the company (then called Micrablate) in 2004, and Brace and Laeseke came on board shortly after. Securing more than $8 million in federal grants, venture capital and private investments, company researchers now are perfecting the Certus 140, an integrated, high-power, high-precision ablation system.
In February 2010, the Wisconsin Department of Commerce included NeuWave on its list of the top-30 second-stage companies to watch in 2010.
Fast fix: Bioactive coating promotes cell growth
For people who suffer excruciating back pain due to injury or disc degeneration, relief often comes in the form of spinal fusion and disc replacement. Metallic implants are the current standard, and while these devices mechanically fix tissue or replace vertebrae, they don’t heal the problem.
Responding to patients’ need for faster, more effective healing is one of the reasons Associate Professor Bill Murphy and colleagues from the University of Michigan founded Tissue Regeneration Systems.
Murphy and Tissue Regeneration Systems co-founders — University of Michigan engineer Scott Hollister, neurosurgeon Frank LaMarca and maxillofacial surgeon Steve Feinberg, and Midwest-based venture capital professional Jim Adox — are developing ways to use bioactive materials to heal soft tissue and bone.
One approach involves designing custom “scaffolds” for reconstructing bone and soft tissue — particularly in maxillofacial reconstruction and spinal fusion. Murphy and colleagues are developing bioactive coatings for scaffolds that can fill in large bone defects. These coatings deliver stem cell types and molecules that encourage and accelerate bone cell in-growth.
Associate Professor Bill Murphy (center), with graduate students Travelle Franklin-Ford (left) and Jae-Sung Lee.
Similarly, Murphy and UW-Madison Orthopedics and Rehabilitation Associate Professor Ben Graf (also BME) and Assistant Professor Geoffrey Baer are coating such existing devices as sutures, screws, suture anchors, tacks and pins for soft-tissue healing. They can apply these coatings to different types of devices and deliver different biological molecules, which can bind in the operating room and release over time as the injured area heals.
In large-animal models, Murphy and UW-Madison Medical Sciences Professor Mark Markel (also BME) have shown they can enhance bone and tendon healing in bone defects with coated biodegradable screws, in the rotator cuff with coated biodegradable sutures, and in other applications.
Based in Ann Arbor, Michigan, Tissue Regeneration Systems secured $2 million in venture capital in 2008 from Madison-based Venture Investors. Funding sources for the research include the UW-Madison Wallace H. Coulter Translational Research Partnership, the Wisconsin Alumni Research Foundation Technology Accelerator Program, and the National Institutes of Health.