“Would you poison the entire garden to kill one weed?” asked Justin Hanes at the opening of his talk at the 2012 Johns Hopkins annual NanoBio Symposium. “Unfortunately, that is how most chemotherapy works today.” Hanes is a professor of ophthalmology at Johns Hopkins School of Medicine and an affiliated faculty member of the Institute for NanoBioTechnology.
On average, less than one percent of any chemotherapy cancer treatment will go to a patient’s tumor. The remaining 99 percent circulates through the rest of the patient’s body, kills healthy cells unnecessarily, and causes often unbearable side effects. This alarming statistic has led Hanes and his team to focus on targeted, chemotherapeutic drug delivery using nanoparticles.
Hanes explained that nanoparticles are ideal in cancer treatment because tumors form new blood vessels within themselves to be able to receive nutrients, and these tumor-associated blood vessels are leaky. Thin, leaky blood vessel walls are ideal for drug-loaded nanoparticles, which are on the order of 1-100 nanometers in diameter, to break through to reach tumor cells. The ultimate goal of nanoparticle drug delivery for cancer is to synthesize bio-targeted particles that provide localized delivery straight to the tumor alone, improving drug effectiveness and reducing undesirable side effects.
Many members of the Hanes lab focus on drug delivery in mucus, which exists in the lining of the lungs, vaginal tract, intestines, and many other organs. Although mucus is essential to prevent viruses and bacteria from entering tissues, its sticky consistency also acts as a barrier to drug-loaded nanoparticles. Hanes’s students are synthesizing nanoparticles that can pass through mucosal barriers.
Scientists previously believed that pores within mucus were around 25 nm in size and that nanoparticles would not be able to pass through. However, the Hanes lab’s work shows that these pores may be closer to 400 nm and that particles with a diameter of 500 nm coated with a simple, biodegradable polymer called PEG can pass through. The PEG gives the particles a neutral charge and makes them hydrophilic, or attracted to water, so that they can pass easily through the mucosal meshwork without getting trapped.
The group is now able to encapsulate chemotherapeutic drugs in mucus-penetrating nanoparticles for a variety of different applications, including lung cancer and ovarian cancer. Additionally, Laura Ensign, an INBT-sponsored graduate student in the Hanes lab, showed in a recently-published journal article that her mucus-penetrating particles effectively delivered drugs in the mouse vaginal tract for longer times than previously reported (>24 h). This work could be applied to cervical cancer, where drug-loaded nanoparticles could be administered to travel through the mucosal lining of the reproductive tract for successful treatment.
Overall, the Hanes lab anticipates that their research will contribute to the effectiveness of many types of cancer treatments. Read more about Ensign’s recently published work here.
Story by Allison Chambliss, a Ph.D. student in the Department of Chemical and Biomolecular Engineering with interests in cellular biophysics and epigenetics.