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|Moreto manufacture, in this case is used to silence the cellular factory, a way of causing apoptosis or cell death. "Si" is shortfor "silence."The lipids also serve as a shield that restricts toxicchemotherapy drugs from leaking from the nanoparticle untilthe protocell binds to and takes hold within the cancer cell.This means that few poisons leak into the system of thehuman host, if the protocells find no cancer cells. Thiscloaking mitigates toxic side effects expected fromconventional chemotherapy.Instead, the particles -- crafted small enough to float under the radar of the liver and other cleansing organs -- cancirculate harmlessly for days or weeks, depending on their engineered size, seeking their prey.A library of phages -- viruses that attack bacteria -- wascreated at UNM's nationally accredited cancer center bycollaborator David Peabody. This permitted researchers toexpose the phages to a group of cancerous cells and normalcells, allowing identification of peptides that bind specifically tocancer cells but not normal cells."Proteins modified with a targeting peptide that binds to aparticular carcinoma exhibit a 10,000-fold greater affinity for that cancer than for other unrelated cells," Ashley said.
Boosting medicine with nanotechnology strengthens drug cocktail many times over
Brinker adds, "A key feature of our protocell is that its fluidbilayer allows high-affinity binding with just a few of thesepeptides overall. This reduces nonspecific binding andimmune response."The method is being tested on human cancer cells in vivo,and will shortly be tested on mouse tumors at UNM's cancer center.The researchers continue to optimize the size of the poroussilica particle, which is formed by aerosolizing a precursor solution. The porous nanoparticle fabrication process -- calledevaporation-induced self-assembly, and pioneered in theBrinker lab -- produces particles from 50 nanometers toseveral microns in diameter. Particle sizes between 50 and150 nanometers in diameter are ideal for maximizingcirculation and uptake into cancer cells, so the particles arepreselected by size before their formation into protocells."Their overall dimensions determine how widely they'll bedistributed in the bloodstream," Brinker said. "We're alteringour synthesis to favor the smaller sizes."Also of importance to the circulation time of the particle are itselectrical charge and hydrophobicity [avoidance of water],which can improve or detract from its ability to remain free of unwanted molecular or energetic entanglements.The method may be commercially available in five years,researchers estimate.Brinker is a Sandia Fellow and UNM Regent's andDistinguished Professor of Chemical and Nuclear Engineeringand member of UNM's cancer center.Other institutions involved in the research include theUniversity of California Davis, and the University of Waterlooin Canada.Funding was provided by the National Cancer Institute (NCI),the National Science Foundation, the Department of Energy'sBasic Energy Sciences program, the Air Force Office of Scientific Research, and Sandia's Laboratory DirectedResearch and Development office.The work is the first to show targeted delivery of nanoparticlesto cancers that is supported in part by a grant from NCI'sAlliance for Nanotechnology in Cancer.
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