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.