{"id":12529,"date":"2017-10-19T08:39:35","date_gmt":"2017-10-19T14:39:35","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=12529"},"modified":"2019-10-14T14:02:18","modified_gmt":"2019-10-14T20:02:18","slug":"cu-researchers-see-golden-opportunity-for-bladder-cancer-patients","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/cu-researchers-see-golden-opportunity-for-bladder-cancer-patients\/","title":{"rendered":"CU researchers see golden opportunity for bladder cancer patients"},"content":{"rendered":"
<\/div>
\"graphic
The team engineered their gold nanorods with receptors that bind with a protein that\u0092s overactive in bladder cancer cells. Once bound, infrared laser light heats up the gold, killing the cancer cells (courtesy Won Park).<\/figcaption><\/figure>\n

All that is gold does not glitter. But if an eclectic University of Colorado team\u2019s work continues to pan out, invisibly tiny bits of gold could one day be the focal point of a revolutionary new bladder cancer treatment.<\/p>\n

A collaboration between cell biologists in the CU School of Medicine in Aurora and laser engineers in the CU Department of Electrical, Computer & Energy Engineering in Boulder has yielded a promising way to attack bladder cancer: Use an infrared laser to heat up gold nanorods specially engineered to bind with bladder cancer cells. The nanorods then fry the rogue cells.<\/p>\n

Thomas Flaig, MD, a urologic oncologist and associate dean for Clinical Research at the CU School of Medicine as well as chief clinical research officer of UCHealth, led the cell-biology effort in Aurora; Won Park, PhD, the N. Rex Sheppard Professor in the Department of Electrical, Computer & Energy Engineering at CU Boulder, spearheaded the nanophotonic work in Boulder.<\/p>\n

Nanophotonic?<\/h3>\n

Park specializes in using light to change the behavior of nanoparticles \u2013 materials measured in terms of a few billionths of a meter, which gets down to the sizes of individual proteins (for perspective: a nanometer is to a meter what a hazelnut is to planet Earth). A decade ago, Park was spending a sabbatical at the University of Colorado Cancer Center, where Flaig specializes in bladder and other cancers. Over coffee, they got to talking.<\/p>\n

\"Dr.
Dr. Thomas Flaig, MD<\/figcaption><\/figure>\n

The treatment for superficial bladder cancer (that is, cancer that hasn\u2019t pierced the bladder\u2019s lining into the muscle, which comprise about 70 percent of cases) hasn\u2019t changed much since the 1980s, Flaig explained. You insert a catheter into the bladder and inject directly onto the tumors a strain of bacteria called BCG, which is also a tuberculosis vaccine. The technique\u2019s ability to directly target cancer in the bladder \u00a0\u2013 unlike, say, chemotherapy, which sloshes about the entire body \u2013 presents a special opportunity in cancer care, and it does work, Flaig said. But given how common bladder cancer is, with about 75,000 new cases a year and about 16,000 deaths in the United States, medical science has been slow to develop alternative approaches.<\/p>\n

\u201cWe really need innovation in bladder cancer,\u201d Flaig said recently. \u201cThis would be a very practical way of delivering cancer therapy through administration of a nanotherapy route.\u201d<\/p>\n

Two facts<\/h3>\n

Park\u2019s work focused on nanotherapy using lasers. The challenge with nanotherapy, though, was that if you infuse nanoparticles like a chemotherapy, the liver tends to clear them out. There were also open questions about possible collateral impacts of unleashing vast schools of nanoparticles into the bloodstream. But here in the bladder was a way to deliver nanoparticles directly to the cancer, and one which would involve the same sort of catheter-based treatment that Flaig and colleagues have used routinely for years in treating bladder cancers. And so the cancer-cell specialist and the laser expert decided to team up.<\/p>\n

The effort hinged on two facts, the first having to do with optical physics, the second with biochemistry. The first was that gold nanorods can be engineered to vibrate and heat up when hit with a specific color of near-infrared light (in this case, Park tuned his nanorods to respond to laser light just a bit redder than the eye can see). In principle, it\u2019s not too different than how your microwave oven warms up a neglected cup of coffee by blasting it with electromagnetic waves tuned to make water molecules vibrate.<\/p>\n

The second fact, having to do with biochemistry, is that bladder cancer cells have a lot more epidermal growth factor protein receptors (EGFRs) poking through their cellular surfaces than healthy cells do.<\/p>\n

The approach<\/h3>\n

The success of Flaig\u2019s and Park\u2019s collaboration would depend on their ability to exploit these two facts. They would have to somehow modify gold nanorods such that they could bind to EGFR receptors and then, once the nanorods were docked with the cancerous cells, hit them with infrared light such that they heated up and cooked while leaving healthy neighboring cells largely be.<\/p>\n

\"Gold
Gold nanorods, as seen through a scanning electron microscope (courtesy Won Park).<\/figcaption><\/figure>\n

Gold, a noble metal, is happy enough to bond to nothing at all, which is why it doesn\u2019t rust. So festooning the nanorods with EGFR antibodies \u2013 essentially molecular keys that fit the EGFR\u2019s molecular lock \u2013 was no easy trick. But by 2014, the team had figured out how to do it using something called pegylation. They called the resulting liquid solution \u201cconjugated gold nanorods\u201d (CGR), which, being a clear or blueish liquid, looks like nothing stored in Fort Knox. They also showed that, in petri dishes, CGR bonded to the EGFR receptors of bladder cancer cells. Now they had to hit it with a laser and show that it would work in living creatures.<\/p>\n

This past August, Flaig, Park and colleagues reported their success with just that. They used mice engineered with bladder cancer to test the effectiveness of laser light on its own (lasers can, after all, do some damage), laser light with straight gold nanoparticles, and laser light with the CGR the team had invented. They found that only the laser-plus-CGR combination killed large numbers of surface bladder cancer cells. So in principle, the approach worked.<\/p>\n

Up next<\/h3>\n

The team has applied for a patent on their conjugated gold nanorods and, as Flaig put it, \u201cwe really have an eye on moving this to a clinical application. We realize that is a big hurdle, but that is our goal.\u201d<\/p>\n

\u201cIt\u2019s a really interesting way of addressing the problem,\u201d Flaig said. Plus, he said, because it would also use catheters \u2013 to empty the bladder, to apply and remove excess CGR solution, and to apply fiber-optic-delivered laser light inside the bladder, \u201cthere\u2019s very little change in the way we\u2019ve treated local bladder cancer for decades\u201d from the patient\u2019s perspective.<\/p>\n

There\u2019s much work to do. Jared Brown, PhD, of CU\u2019s Skaggs School of Pharmacy, has joined to the team. He specializes in nanotoxicology, expertise that will be vital in proving the approach\u2019s safety before it can win U.S. Food and Drug Administration approval to start testing their exquisitely engineered nanorods in people. They also must establish how exactly the laser light and the golden solution will work in the human body, how thoroughly the technique will kill cancer cells, how the approach impacts adjacent healthy tissue, and how they\u2019ll go about producing (or having someone else produce) enough CGR for clinical trials, among other things. Despite the challenges ahead, Flaig is optimistic that the long march from lab to clinic will yield better treatment for bladder cancer patients at UCHealth and beyond.<\/p>\n

In the meantime, he says, he is enjoying what he described as \u201ca fun and ongoing collaboration\u201d among his and Park\u2019s CU teams, who despite \u201calmost no overlap in expertise\u201d have produced a string of successes neither could have hoped for alone.<\/p>\n

\u201cTo me, that\u2019s one of the neatest parts of the whole project,\u201d Flaig said.<\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

All that is gold does not glitter. But if an eclectic University of Colorado team\u2019s work continues to pan out, invisibly tiny bits of gold could one day be the focal point of a revolutionary new bladder cancer treatment. A collaboration between cell biologists in the CU School of Medicine in Aurora and laser engineers […]<\/p>\n","protected":false},"author":23,"featured_media":20360,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[5],"tags":[49,4781,2312],"class_list":["post-12529","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innovative-care","tag-cancer-treatment","tag-research-in-health-care","tag-uchealth-university-of-colorado-cancer-center"],"acf":[],"yoast_head":"\nGolden opportunity for new bladder cancer treatment - 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