California's Nano Sensing Δ 8th of September 2014 Ω 11:15 PM

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~ UC SanDiego Researchers Target Tumors with Nanoworms ~ UC SantaBarbara MCDB ~ sense for Ξ	~ sense for Ξ ~ sense for Ξ ~ sense for Ξ	~ sense for Ξ ~ sense for Ξ ~ sense for Ξ
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«U.S. Nano Sensing	Θ	Θ
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~ UCSanDiego Researchers Target Tumors with Nanoworms

»UCSanDiego Researchers Target Tumors with Nanoworms

ξ Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized �nanoworms�
ξ they can cruise through the bloodstream without significant interference from the body�s immune defense system
ξ like tiny anti-cancer missiles�home in on tumors
ξ segmented �nanoworms� composed of magnetic iron oxide and coated with a polymer are able to find and attach to tumors
ξ their discovery is detailed in this week�s issue of the journal Advanced Materials
ξ is reminiscent of the 1966 science fiction movie, the Fantastic Voyage,
ξ in which a submarine is shrunken to microscopic dimensions,
ξ then injected into the bloodstream to remove a blood clot from a diplomat�s brain

ξ using nanoworms, doctors should eventually be able to target and
ξ reveal the location of developing tumors
ξ that are too small to detect by conventional methods

ξ carrying payloads targeted to specific features on tumors,
ξ these microscopic vehicles
ξ could also one day provide the means to more effectively deliver toxic anti-cancer drugs
ξ to these tumors in high concentrations without negatively impacting other parts of the body

ξ �Most nanoparticles are recognized by the body's protective mechanisms,
ξ which capture and remove them from the bloodstream within a few minutes,�
ξ said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team.

ξ �The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces
ξ that allows the nanoworms to evade these natural elimination processes
ξ As a result, our nanoworms can circulate in the body of a mouse for many hours.�

ξ �When attached to drugs, these nanoworms could offer physicians
ξ the ability to increase the efficacy of drugs
ξ by allowing them to deliver them directly to the tumors,�
ξ said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at MIT who was part of the team.
ξ �They could decrease the side effects of toxic anti-cancer drugs
ξ by limiting their exposure of normal tissues and
ξ provide a better diagnosis of tumors and abnormal lymph nodes.�

ξ The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together,
ξ like segments of an earthworm,
ξ to produce tiny gummy worm-like structures about 30 nanometers long�or about 3 million times smaller than an earthworm

ξ Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI,
ξ or magnetic resonance imaging, machines that are used to find tumors

ξ �The iron oxide used in the nanoworms has a property of superparamagnetism,
ξ which makes them show up very brightly in MRI,� said Sailor.
ξ �The magnetism of the individual iron oxide segments, typically eight per nanoworm,
ξ combine to provide a much larger signal than can be observed if the segments are separated.
ξ This translates to a better ability to see smaller tumors,
ξ hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.�

ξ In addition to the polymer coating,
ξ which is derived from the biopolymer dextran,
ξ the scientists coated their nanoworms with a tumor-specific targeting molecule,
ξ a peptide called F3,
ξ developed in the laboratory of Erkki Ruoslahti,
ξ a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara
ξ this peptide allows the nanoworms to target and home in on tumors

ξ �Because of its elongated shape,
ξ the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,� said Sailor.
ξ �And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.�

ξ The scientists were able to verify in their experiments
ξ that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and
ξ following the aggregation of the nanoworms on the tumors.
ξ They found that the nanoworms,
ξ unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system,
ξ remained in the bloodstream for hours.

ξ �This is an important property because the longer these nanoworms can stay in the bloodstream,
ξ the more chances they have to hit their targets, the tumors,� said Ji-Ho Park,
ξ a UC San Diego graduate student in materials science and engineering working in Sailor�s laboratory.

ξ Park was the motivating force behind the discovery
ξ when he found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream
ξ despite their relatively large size.

ξ While it�s not clear yet to the researchers why, Park notes that
ξ �the nanoworm�s flexibly moving,
ξ one dimensional structure may be one the reasons for its long life in the bloodstream.�

ξ The researchers are now working on developing ways to attach drugs to the nanoworms and
ξ chemically treating their exteriors with specific chemical �zip codes,�
ξ that will allow them to be delivered to specific tumors, organs and other sites in the body.

ξ �We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,� said Ruoslahti
ξ We hope that these devices will improve the diagnostic imaging of cancer and
ξ allow pinpoint targeting of treatments into cancerous tumors.�

ξ Other researchers involved in the development were
ξ Michael Schwartz of UC San Diego,
ξ Geoffrey von Maltzahn of MIT, and
ξ Lianglin Zhang of UC Santa Barbara

ξ The project was funded by grants from the National Cancer Institute of the National Institutes of Health.

ξ Media Contact: Kim McDonald, 858-534-7572
ξ Comment: Michael Sailor 858-534-8188

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~ UCSantaBarbara MCDB

»Univeristy of California Santa Barbara Molecular Cellular and Development Biology

Burnham Institute for Medical Research Announces Affiliation with UC Santa Barbara
ξ Burnham-UCSB is now home to 'Vascular Mapping Center' founded by Burnham's Distinguished Professor, Erkki Ruoslahti, M.D., Ph.D.
ξ The Burnham Institute for Medical Research ("Burnham") has established an affiliation with the University of California, Santa Barbara
ξ it's led by internationally renowned medical researcher Erkki Ruoslahti, M.D., Ph.D.
ξ Dr. Ruoslahti maintains his primary appointment as distinguished professor with Burnham
ξ he joins UCSB's Department of Molecular, Cellular and Developmental Biology as an adjunct distinguished professor

ξ At Burnham-UCSB, Ruoslahti has opened the "Vascular Mapping Center"
ξ center will focus on developing applications for vascular "zip codes," based on technology discovered in his laboratory
ξ Vascular zip codes are molecular signatures in blood and lymphatic vessels ("vasculature")
ξ that are specific to individual tissues and disease sites
ξ Ruoslahti has discovered ways to selectively target drugs to tumor blood vessels in mice and suppress the growth of those tumors
ξ he has also found a way to selectively target the lymphatic vessels in tumors
ξ the hope is that this very specific delivery of therapeutics to tumor blood and lymphatic vessels
ξ will increase the efficacy of cancer therapies and decrease side effects

ξ Targeting peptides discovered in Ruoslahti's laboratory
ξ are providing the platform for integrating nanotechnologies
ξ into the design of new therapies for cancer and heart disease

ξ Ruoslahti and others at Burnham contribute a key component to the Center of Cancer Nanotechnology Excellence at the University of California, San Diego
ξ founded with $20 million from the National Cancer Institute
ξ a partnership of 25 scientists, primarily from Burnham and UCSB,
ξ has been recognized by the National Institutes of Health as a Program of Excellence in Nanotechnology
ξ with a $13 million grant to design nanotechnologies that
ξ detect,
ξ monitor,
ξ treat, and
ξ eliminate "vulnerable" plaque,
ξ the probable cause of death in sudden cardiac arrest

ξ "Nanotechnology is an expanding emphasis in my research," said Ruoslahti.
ξ "The opportunity to work more closely with our collaborators at UCSB
ξ was a key consideration in choosing this location for our Vascular Mapping Center and forging a Burnham affiliation."

ξ "It is a tremendous advantage to UCSB to have a scientist of Ruoslahti's caliber here,"
ξ said Martin Moskovits, Dean of Mathematical, Life and Physical Sciences
ξ "We feel the Burnham Institute will extend our medical research capability and greatly enhance our students' experience here."

ξ Added Dennis O. Clegg, professor and chair of the Department of Molecular, Cellular and Developmental Biology:
ξ "It's really exciting to welcome Dr. Ruoslahti as a member of the MCDB faculty
ξ He brings a rich tradition of cell biology research along with vigorous, new interdisciplinary investigations of cancer biology
ξ that include many collaborations with UCSB scientists."

ξ Burnham-UCSB was created through a collaborative effort of
ξ the Burnham Institute for Medical Research, based in La Jolla, California, and
ξ the University of California at Santa Barbara

ξ This type of collaboration, involving a highly ranked university and nonprofit, independent research institute,
ξ exemplifies the inherent value of interdisciplinary research and the enhanced potential created when two such entities join force.

ξ Erkki Ruoslahti, M.D. Ph.D., joined Burnham in 1979 and
ξ served as its President and CEO from 1989 through December 2001,
ξ at which time he was appointed distinguished professor.
ξ Dr. Ruoslahti is a member of the U.S. National Academy of Sciences, the Institute of Medicine, American Academy of Arts and Sciences, and
ξ the European Molecular Biology Organization.
ξ He has been recognized internationally with many honors, including
ξ Canada's Gairdner International Award and the 2005 Japan Prize in Cell Biology.

Erkki Ruoslahti, M.D.,Ph.D.
ξ earned his M.D. and Ph.D. from the University of Helsinki in Finland in 1967
ξ after postdoctoral training at the California Institute of Technology,
ξ held various academic appointments with the University of Helsinki and the University of Turku in Finland and City of Hope National Medical Center in Duarte, California
ξ joined The Burnham Institute in 1979
ξ served as its President from 1989-2002
ξ has been a Distinguished Professor at UCSB in Biological Sciences since 2005
ξ elected membership to the U.S. National Academy of Sciences, Institute of Medicine, American Academy of Arts and Sciences, and the European Molecular Biology Organization
ξ is the recipient of the G.H.A. Clowes Award, Robert J. and Claire Pasarow Foundation Award, Jacobaeus International Prize,
ξ The Jubilee Award given by the British Biomedical Society
ξ was a Nobel Fellow at the Karolinska Institute in Stockholm in 1995
ξ is an Honorary Doctor of Medicine from the University of Lund
ξ a Knight of the Order of the White Rose of Finland
ξ is the recipient of the 2005 Japan Prize in Cell Biology
ξ Contact Information: Phone: (805) 893-5327 Fax: (805) 893-5805 E-Mail: ruoslahti@burnham.org

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