Resolve - Volume 1, 2012 - (Page 2)
BIOBRIEFS Turning a tumor’s weapon against itself
Understanding the building blocks of biochemistry and structural biology, says Bryan Berger, can lead to creative solutions to medical mysteries. Berger studies protein structure and molecular recognition and is particularly interested in how cell receptors switch on and off in relation to disease and how engineered peptides function in the body to combat disease. He and Mark Snyder, both assistant professors chemical engineering, are developing nanoscale packages that, like smart bombs, release chemotherapy drugs at the site of a rapidly growing tumor while limiting the drugs’ toxic effects on healthy tissues. Normally growing cells feed off oxygen delivered through tiny blood vessels in tissue. When a precancerous cell morphs into a cancerous state, it grows at a rate faster than the oxygen supply can support. It then adjusts its metabolism to consume sugars stored in the cells and grow anaerobically. This anaerobic metabolism causes the tumor cells to secrete enzymes called proteases that devour adjoining tissue to make room for the cancer’s rapid proliferation. The process produces lactic acid, which lowers the pH around the tumor site. Berger synthesizes peptides (sequences of amino acids) and programs them to use the tumor’s protease weapons against itself. “My lab designs peptides that the protease secreted by a specific cancer act upon,” he says. Utilizing knowledge about the types of amino acid bonds that a specific protease will attack, and the size and shape of molecules that can penetrate the diseased tissue, Berger develops a peptide that will fold or change shape when it senses the tumor’s enzymes and lowered pH. Snyder incorporates the peptide into a silica-based nanoparticle package that encapsulates a small amount of an effective anti-cancer drug. The package is designed so that in the low-pH tumor environment, the peptide unfolds and is cleaved by protease, which causes the nanopackage to release the drug where it is needed. “Most cancer drugs are effective but toxic,” Berger says. “We want to keep them stable, shield them and release them at the right time.” Other organic, polymer-based approaches to packaging chemotherapy drugs exist, he says, “but the polymers are much more susceptible to degradation and have shorter half-lives than silica, which is inorganic and much more resilient.” Berger and Snyder have a grant from the Pennsylvania Department of Health’s Commonwealth Universal Research Enhancement (CURE) program. They collaborate with Ellen Puré, professor of molecular and cellular oncogenesis at the Wistar Institute, a cancer research center in Philadelphia.
A sensitive peptide triggers a nanoscale package to release drugs at cancer sites. View larger ►
New adsorbent combats both arsenic and fluoride
Two of the world’s most harmful groundwater contaminants are arsenic and fluoride. Chronic consumption of water with excessive levels of fluoride can cause pain and damage to bones and joints and other symptoms. The consequences of arsenic are more severe and include skin lesions, cancer and even death. Scientists estimate that as many as 500 million people in Africa and Asia consume groundwater that is naturally contaminated by one of the two toxins, says Arup K. SenGupta, professor of civil and environmental engineering and also of chemical engineering. SenGupta and Surapol Padungthon, a Ph.D. student, have developed an adsorbent that can remove both arsenic and fluoride. The adsorbent is reusable and takes advantage of the unique
the development of the adsorbent through lab and field work in areas whose groundwater is surface properties of metal oxide nanoparticles. contaminated with fluoride or arsenic. The two SenGupta has a Fulbright Environmental contaminants, he says, rarely occur together. Leadership Award to spend six months in the Center The award will also enable SenGupta to for Sustainable Technologies at build on the success of an inexpenthe Indian Institute of Science in sive filtration system that removes Bangalore, India. arsenic from groundwater at the The project is titled “Mitigating wellhead. The system has been Fluoride and Arsenic Crisis.” installed in more than 200 villages The award SenGupta received is in eastern India and is also in use called the Fulbright-Nehru Grant in the U.S., Hungary, Ecuador and and is named for Jawharlal Brazil. A patent for the system was Nehru, the first prime minister awarded to SenGupta and Luis of independent India. Cumbal ’05 Ph.D., who is now The grant will enable SenGupta Arup SenGupta’s first Sustainable director of graduate studies at the Arsenic Removal System was to collaborate with scientists and Army Engineering Polytechnic School installed in India in 2004. engineers in India to streamline in Quito, Ecuador.
2 • RESOLVE • A FOCUS ON LEHIGH ENGINEERING
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