Tiny structures, big impact

By: Sarah DeWeerdt
Photos: Dennis Wise / University of Washington
Top image:  Immunostained neuron stem cells.

Lots of people in Seattle enjoy seafood. But Miqin Zhang has a different sort of appreciation for shrimp and crabs than most: one of her longtime passions is chitosan, a long molecule with a backbone of carbon atoms that is a component of the hard outer skeleton of shellfish.

“Chitosan is really magical,” says Zhang, a professor of materials science and engineering and of neurological surgery. “It's very biocompatible, and it has a lot of functional groups.” These characteristics make chitosan-based materials safe to use inside the human body and offer flexibility for engineers like Zhang to manipulate the molecule in myriad ways.

Zhang uses chitosan to build nanoparticles — tiny structures barely thousandths of a hair-width in size, too small to be seen with a conventional microscope — for use in cancer therapy. A member of the Institute for Nano-Engineered Systems, she’s one of several researchers across the UW working in the rapidly growing area of nanotherapeutics — the use of nanomaterials to diagnose, treat and monitor disease.

In lab tests, Zhang and her team have found that paclitaxel-loaded nanoparticles inhibit mammary tumor growth and prevent its spread better than the standard formulation of paclitaxel. The nanoparticles stay in the bloodstream more than 12 times longer than the standard formulation and show no evidence of toxicity — unlike the solution used in the standard formulation, which can cause liver damage.

Zhang began working with nanomaterials over a decade ago, when the field was in its infancy. “I wanted to do something new, very new — pioneer,” she says.

The attraction to cancer medicine was more personal. Many of Zhang’s female relatives have had breast or other cancers, and two of her aunts died from the disease in their 30s, leaving young children behind. “It’s kind of painful,” she says. Working on cancer drug delivery offered a way to combine her intellectual passions with the potential to help cancer patients like her family members.

Advancing efforts with multifunctional materials

In addition to chitosan, Zhang’s team has constructed nanoparticles from a variety of other materials. “We’re particularly interested in iron oxide nanoparticles because they are biocompatible, biodegradable and detectable in magnetic resonance imaging (MRI),” she says.

This offers the opportunity to combine multiple functions in one tiny structure: both imaging and drug delivery. For example, a nanoparticle formulation with a hollow shell coating of iron oxide nanoparticles and chitosan, and cargo of the chemotherapy drug doxorubicin shrinks tumors in mice and also kills cancer cells growing in laboratory dishes, the team has reported. That effort involved a unique method of nanoparticle assembly: the researchers essentially deposited the drug into the hollow shell of the structure rather than trying to inject the fragile drug molecule into a completed particle. The iron oxide nanoparticles then triggered on-demand drug release using an external magnetic field.

Iron oxide nanoparticles show no evidence of toxicity or immune system activation in a lab study conducted by Zhang’s team. That study also demonstrated that MRI can reliably track the distribution and spread of nanoparticles in the body, providing a tool that could aid in bringing them into the clinic.