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Nano Particles With Honeycomb Cavities Containing Drugs Blast Cancer Cells

Nano Particles With Honeycomb Cavities Containing Drugs Blast Cancer Cells

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Published by Dr. Bob Glass
delivering using nano particles
delivering using nano particles

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Published by: Dr. Bob Glass on Apr 22, 2011
Copyright:Attribution Non-commercial


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4/22/11 10:41 AMNano Technology Group News | LinkedInPage 1 of 3http://www.linkedin.com/news?viewArticle=&articleID=483537004&g…114208%2Ehtm&urlhash=YKsF&goback=%2Egde_1031077_member_51243124
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Lung Cancer Cancer Prostate Cancer 
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NanotechnologyBiochemistryOrganic Chemistry
NanomedicineNatural killer cellNanoparticleMonoclonalantibody therapy
ScienceDaily (Apr. 20, 2011)
— Meldingnanotechnology and medical research, SandiaNational Laboratories, the University of NewMexico, and the UNM Cancer Research andTreatment Center have produced an effectivestrategy that uses nanoparticles to blast cancerouscells witha mélange of killer drugs.
In the cover article of the May issueof 
Nature Materials
, available onlineApril 17 , the researchers describesilica nanoparticles about 150nanometers in diameter ashoneycombed with cavities that canstore large amounts and varieties of drugs."The enormous capacity of thenanoporous core, with its highsurface area,combined with theimproved targeting of anencapsulatinglipid bilayer [called aliposome], permit a single 'protocell'loaded with a drug cocktail to kill adrug-resistant cancer cell," saysSandia researcher and UNMprofessor Jef Brinker, theprincipal investigator."That's a millionfold increase in efficiency over comparable methods employingliposomes alone -- withoutnanoparticles -- as drug carriers."The nanoparticles and thesurrounding cell-like membranesformed from liposomes together become the combinationreferred to as a protocell: the membrane seals in the deadlycargo and is modified with molecules (peptides) that bindspecifically to receptors overexpressed on the cancer cell'ssurface. (Too many receptors is one signal the cell iscancererous.) The nanoparticles provide stability to thesupported membrane and contain and release the therapeuticcargo within the cell.A current Food and Drug Administration-approvednanoparticle delivery strategy is to use liposomes themselvesto contain and deliver the cargo. In a head-to-headcomparison of targeted liposomes and protocells with identicalmembrane and peptide compositions, Brinker and colleaguesreport that the greater cargo capacity, stability and targetingefficacy of protocells leads to many times greater cytotoxicity[destruction] directed specifically toward human liver cancer cells.Another advantage to protocells over lipsomes alone, sayslead author Carlee Ashley, a Harry S. Truman post-doctoralfellow at Sandia's California site in Livermore, is thatliposomes used as carriers need specialized loadingstrategies that make the process more difficult. "We'vedemonstrated we can just soak nanoparticles to load themwith unique drug combinations needed for personalizedmedicine. They effectively encapsulate toxins as well assiRNA [ribonucleic acid] that silence expressions of proteins."RNA, the biological messenger that tells cells which proteins
The figure on the left (Hep3B) shows a greenly fluoresced cancerous liver cell penetrated by  protoc ells. The small red dots are lipid bilayer wrappi ngs. Their cargo — drug-fill ed nanoparticles,their pores here filled with white f luorescent dyes for i maging purposes — penetrat e the cancerous cell.(P enetration is more clearly seen in the second image.) The normal cell on the right (hepatocyte) shows no penetration. (Credit: Imagecour tesy of DOE/Sandia National Laboratories)
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4/22/11 10:41 AMNano Technology Group News | LinkedInPage 2 of 3http://www.linkedin.com/news?viewArticle=&articleID=483537004&g…114208%2Ehtm&urlhash=YKsF&goback=%2Egde_1031077_member_51243124
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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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