As far back as the 4th Century B.C., Aristotle marveled at the nimble gecko's ability to "run up and down a tree in any way, even with the head downwards."
Its grippy toes, able to latch on to even the slipperiest surface with extraordinary force, have inspired everything from super glues to "Superman" climbing suits to sponges for soaking up environmental toxins.
Now CU Boulder scientists have taken a cue from the reptile to develop a material able to stick to tumors inside the body, pumping out chemotherapy drugs for days.
The technology, developed with doctors at the University of Colorado Anschutz Medical Campus, i s described in the journal Advanced Materials.
"Nature has been at this for millions of years and offers clues for developing better biomaterials," said senior author Wyatt Shields, Thomas F. Austin assistant professor of Chemical and Biological Engineering at CU Boulder.
First-author Jin Gyun Lee, a postdoctoral researcher in the Shields Lab, said early results show great promise.
"We envision that this gecko-inspired technology could ultimately reduce the frequency of clinical treatments, potentially allowing patients to receive fewer but longer-lasting therapies," Lee said.
The power of sticky toes
The gecko's secret to effortlessly ascending surfaces as smooth as glass lies in the millions of microscopic, hair-like fibers, called setae, that line their toes.
With each step, these structures — and thousands of even tinier split ends called spatulae — flatten out across a broad surface area, conforming into nooks and crannies.
When molecules on the spatulae and surfaces interact— a phenomenon known as Van der Waals force— their feet stick hard. Yet just a slight movement can break the bond, enabling them to scurry on.
Scientists have tried for decades to replicate the design of the gecko toe, for use in stronger adhesives, medical and personal care products, and more. But those tiny hairs have proven complicated and expensive to fabricate and almost impossible to make at scale.
Shields and Lee sought to invent a material that was not only sticky, but could also linger safely in the body, delivering a sustained dose of medicine, before disintegrating.
They developed a way to turn an already FDA-approved biodegradable polymer, poly lactic-co-glycolic acid (PLGA), into small particles displaying branched hair-like nanostructures similar to those on the gecko's feet.
Then they infused these "soft dendritic particles" with chemotherapy drugs and attached them to cancer cells in a petri dish and bladder tumors in mice.
They found that the particles clung tightly to the cancer for days, even in a slippery environment like the surface of a bladder. The animals tolerated them well and elicited a favorable immune response.
"We've developed a practical, flexible platform for localized cancer therapy that could be easily scaled and translated," said Lee.
The challenge with bladder cancer
The authors stress that more research is necessary, and it could be years before the technology is ready for clinical trials in people.
Ultimately, they say, it could be a game changer for treating localized tumors, with minimal damage to surrounding healty tissue.
The team started with bladder cancer because it can be uniquely challenging to treat.
"Bladder cancer is common, with most patients presenting with localized disease," said co-author Thomas Flaig, MD, an oncologist and professor of medicine at CU Anschutz who specializes in bladder cancer. "There is a real need for new and effective therapies to prevent progression to more advanced stages of disease for these patients."
To treat localized bladder tumors, doctors typically insert a catheter into the bladder and bathe the organ in chemotherapy drugs. Because people urinate about six times a day, the medication washes out fast, necessitating frequent repeat treatments that can be painful.
Side effects are common, since the drugs hit the healthy tissue, too. Often, the cancer comes back.
The researchers envision a day when a gel containing their gecko-inspired particles could be applied directly to the tumor, delivering a sustained, high concentration of cancer-killing medicine more selectively to the tumor until it breaks down and is excreted.
The technology could also work for other cancers, such as oral, head or neck tumors.
The team of biomedical and materials engineers, medical oncologists and cancer biologists plan to continue their cross-campus collaboration — and look to nature for inspiration.
