Cancer & Nanoparticles
The Incredible Potential of the Nanoparticle
Just before cancer researcher Lily Yang received her medical degree from West China University in 1983, she saw a patient hospitalized with pancreatic cancer. Surgery wasn’t helpful and the patient was in severe pain, which Yang tried to combat with pain meds. After a few long nights, the patient died. "That's when I realized I wanted to be a researcher," Yang says, on an early spring day in her office at Winship Cancer Institute, which overlooks the CHOA heliport. "I wanted to fight cancer on a different level, not watch people suffer like that."
After earning a PhD in molecular and cell biology and biochemistry at Brown University and post doctoral training at University of South California, Yang came to Emory, where she is a professor of surgery and radiology and the Nancy Panoz Chair of Surgery in cancer research. As one of the most well funded researchers in the department, her goal is to apply nanotechnology to fight disease in the emerging field of nanomedicine.
Nanomedicine's secret weapon is its size, since it uses particles as small as antibodies or viruses to create molecular imaging probes and drug-carriers for in vivo delivery. Imaging with nanoparticles may help expose cancer before health has deteriorated, says Yang, and help guide surgeons in their efforts to detect, treat, and remove tumors.
Yang's current research focuses on developing multifunctional, tumor-targeting nanoparticles. Yang and colleagues have developed a magnetic iron oxide nanoparticle platform for molecular tumor imaging and targeted cancer therapy that is able to detect primary and metastatic tumors in breast, pancreatic, and ovarian cancers in animal models.
"I've been working in therapeutic nanoimaging for more than ten years," says Yang, who has worked closely with Shuming Nie, of the Coulter Department of Biomedical Engineering, and radiologist Hui Mao, on the use of nanoparticles to illuminate tumor boundaries and cancer cells. "So now, one of the major concerns is how to efficiently deliver therapeutic agents to the tumor. We thought nanoparticles might offer a new approach."
Chemotherapy and radiation are clearly broad sweeps, killing cancer cells at a cost. But imagine a nanoparticle that carries a drug directly to the tumor site, works around any obstacles, and binds to the cancer cells, and only the cancer cells, before dispensing its medication.
These targeted, multifunctional nanoparticles are a reality, although they have only been tested using human tumor cells and tumor tissues obtained from human patients in mice so far. Ideally, the nanoparticle could serve multiple roles, delivering imaging agents, medications, and monitoring treatment responses. "Only a nanoparticle can deliver two drugs together to the same tumor cell at the same time, which offers an opportunity to kill drug resistant tumor cells," Yang says.
In one of her studies targeting pancreatic cancer lesions, she was able to use the nanoparticle to specifically target the cancer tissue through a protease enzyme receptor (uPAR) that cancerous tumors and metastases produce but healthy pancreatic tissue does not. Using such a specific targeting mechanism allows targeted nanoparticles to detect cancer cells that have spread from the tumor but are still too small to be seen.
"People are living longer today because of early detection, but cancer is still a challenge because it’s so heterogeneous," Yang says, "In a single patient with pancreatic cancer, there are more than 63 genetic alterations."
The targeting mechanism in the nanoparticle could interact with multiple cell types within the tumor so that the nanoparticle drugs are able to treat cancer cells and tumor environments that support the tumor growth. This would also allow doctors to avoid systemic toxicity, and the nanoparticles and medicines could be biodegradable, so they could be harmlessly flushed out of the body once their purpose had been served.
“Dr. Yang is constantly looking for ways to innovate the nanoparticle delivery platform, whether through unique targeting molecules, unique dyes, or unique linkers that release drugs only under certain cellular conditions,” says Emory Office of Technology Transfer Licensing Associate Cliff Michaels. “This mix and match approach allows for the tailoring of her nanoparticle compositions so they have the particular qualities needed to address a certain tumor type. It’s quite a clever strategy.”
Even if a cancer has become drug resistant, multiple medicines could be tried more easily with nanoparticle delivery, and tumors might be able to be reduced enough to be surgically removed using nanoparticle imaging probe-guided surgery. Take triple negative breast cancer, Yang says: It’s often detected at the later stages, the tumors are highly aggressive, and about half of the patients are highly resistant to chemotherapy. Or pancreatic cancer: the cancer creates both physical and intrinsic barriers (like tumor stroma) that reduce drug delivery and promote cancer cell survival, and 85% of patients aren’t candidates for curative surgery. “Personalized therapy is necessary for effective cancer treatment,” she says. “And nanoparticles offer one of the best chances we have for truly personalized therapy.”
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