Drugs travel through our bloodstreams into every corner of our bodies — both where they’re needed and where they’re not — and can cause potentially dangerous side effects in healthy tissues or organs.

OUR SOLUTION: Get drugs to exactly where they’re needed.

Illustration: Brian Stauffer

How can we make sure drugs affect only sick cells and not healthy ones?

Chemotherapy drugs attack fast-growing cancer cells, but these drugs are not discerning; they attack fast-growing healthy cells, too. Luckily, tiny functional differences separate healthy cells from cancer cells. By finding and exploiting those differences, it may be possible to create molecular machines that set out to find sick cells, infiltrate them, and only then release the drug, thus sparing healthy tissues. Because cancerous cells have abnormal amounts of free-floating iron, Adam Renslo, PhD, co-director of the Small Molecule Discovery Center, realized cancer drugs could be improved by inserting them into molecular envelopes that require the presence of iron to open.

Renslo’s method lays the groundwork for treatments that reach only cancerous cells, allowing health care providers to use smaller doses of cancer-fighting medicines and still achieve the same therapeutic effect — but with fewer side effects — compared to existing methods of chemotherapy delivery.

Photos: Elisabeth Fall (left, middle); Steve Babuljak (right)

How can we design molecules nimble enough to negotiate the body’s obstacle course?

Our bodies control which substances can enter our tissues, whether the destination is an organ like the brain or a specific type of cell. When designing a potential new drug for a given disease, scientists must ensure that it is physically capable of both penetrating the body’s defenses and being accepted by its target once it arrives. Matthew Jacobson, PhD, is working to overcome this challenge using novel molecules called peptide macrocycles, which are capable of penetrating the biological membranes that separate tissues and cells. For all their girth, macrocycles are especially nimble.

Jacobson’s approach involves engineering small “hinges” into macrocycles, allowing them to fold into specific shapes to pass through the body’s various barriers. He’s shown how tweaks to a class of these molecules can be used not only to ensure their passage through the gut and into the bloodstream, but also to improve their ability to inhibit a certain receptor, called CXCR7, that plays important roles in the development of heart disease and cancer.

How can we pinpoint and control drug delivery over time?

A good drug is less than ideal if it’s hard to use. Nanotechnology-based drug delivery vehicles, placed inside the body, can eliminate the need for patients to administer drugs themselves on a tight schedule. These vehicles can also deliver drugs continuously, maximizing their effectiveness. Anti-glaucoma drugs are a case in point. Glaucoma is currently treated using liquid drops that reduce pressure in the eye, but elderly patients struggle to administer the drops correctly and on the right schedule.

Tejal Desai, PhD ’98, has engineered a tiny implant that slowly releases a controlled amount of the pressure-reducing drug — from within the eye — sparing glaucoma patients from daily eye-drop regimens. And she’s applying the same concept to the prevention and treatment of HIV/AIDS as well. Compared to men, women experience a higher risk of contracting the HIV virus if they miss taking their preventive medications. The Desai lab is creating a biodegradable drug delivery device, that’s inserted under the skin, to solve this problem. This may help arrest the spread of HIV globally, especially among women.