Dual-Purpose Nanoparticles Spot Residual Tumors, Improves Cancer Surgery

March 24, 2010, National Cancer Institute

(PhysOrg.com) -- The surest cure for cancer is to remove every last bit of a tumor through surgery. Unfortunately, for most cancers that is also the most difficult approach because of two problems: it is nearly impossible today to spot every last tumor in the body and it is often difficult to determine where a tumor stops and healthy tissue begins. A solution to both of those problems may be at hand in the form of a dual-purpose nanoparticle that penetrates tumor cells and lights them up using either fluorescence imaging or magnetic resonance imaging (MRI).

A team of investigators led by Roger Tsien, Ph.D., a member of the National Cancer Institute-funded Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego, developed a dual-purpose nanoparticle that only enters cells coated with two proteins that tumor cells use to invade healthy tissue. Once the nanoparticles accumulate in tumor cells, they become readily visible using either MRI or a standard . The researchers report that they can spot tumors as small as 200 microns in diameter, and that they can then remove even microscopic traces of by tracking the fluorescent signal the nanoparticles emit. Dr. Tsien and his colleagues report their work in back-to-back papers appearing in the .

The investigators built their probe using a spherical polymeric nanoparticle known as a dendrimer. Dendrimers have numerous chemical linkages available on their surface, which enabled Dr. Tsien's team to attach three different entities to each nanoparticle: an activatable cell penetrating peptide (ACPP); three molecules of the brightly fluorescent dye known as Cy5; and 15-30 molecules of gadolinium chelate, a potent MRI contrast agent, to each nanoparticle.

ACPPs are short, positively charged peptides linked by a cleavable molecule to a second negatively charged peptide. Positively charged peptides are well-known for their ability to penetrate cells, but in the inactivated state the linked negatively charged peptide blocks cell penetration. Cleaving the linker removes the negatively charged peptide, allowing the remaining positively charge peptide - and any attached cargo - to enter cells. In this case, the linker is cleaved only by one of two proteins - matrix metalloprotein-2 or matrix metalloprotein-9 - that are present in large numbers on the surfaces of tumor cells. As a result of this specificity, nanoparticles attached to this ACPP only enter tumor cells. Nanoparticles attached to a similar peptide, but one that cannot be cleaved, did not enter and were cleared rapidly from the body.

When injected into animals bearing human tumors, the nanoparticles accumulated in tumors over 48 hours and were readily visible using whole body MRI. When the investigators were conducting this experiment, they noticed bright edges surrounding even small tumors. Upon closer examination using fluorescence microscopy, the researchers were able to clearly delineate the jagged edges of tumors.

Using the bright fluorescent edges as a guide, the investigators were then able to achieve more complete tumor removal than was possible without nanoparticle guidance. Tumor-bearing mice who received the prior to surgery had better long-term tumor-free survival and overall survival than did animals whose tumors were removed using traditional bright-light illumination. The investigators were documented using followup MRI that they had removed all tumors during surgery.

This work is detailed in two papers. The first is titled, "Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases," and the second it titled, "Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival."

Explore further: Self-Assembling Nanoparticles Image Tumor Cells

Related Stories

Self-Assembling Nanoparticles Image Tumor Cells

July 23, 2007

By taking advantage of the full range of ways in which molecules can interact with and bind to one another, a team of investigators at the Carolina Center of Cancer Nanotechnology Excellence has created nanoparticles that ...

Nanoparticles Designed for Dual-Mode Imaging

December 18, 2006

Nanoscale, inorganic fluorescent imaging agents such as quantum dots have become an important tool for researchers studying key biomolecules involved in cancer. At the same time, magnetic iron oxide nanoparticles are proving ...

Fluorescent probes light up cancerous tumors

February 16, 2010

Building on his Nobel Prize-winning work creating fluorescent proteins that light up the inner workings of cells, a team of researchers led by Howard Hughes Medical Institute investigator Roger Tsien, PhD, professor of pharmacology, ...

Nanoparticles Image Breast Cancer

July 21, 2009

Current methods of detecting breast cancer suffer from low sensitivity, limited spatial resolution, or the need to use complicated and expensive radioisotope-based technologies. A new report from investigators at the Emory-Georgia ...

Multifunctional Nanoparticles Image and Treat Brain Tumors

December 4, 2006

Combining two promising approaches to diagnosing and treating cancer, a multidisciplinary research team at the University of Michigan has created a targeted multifunctional polymer nanoparticle that successfully images and ...

Protein Cage Helps Nanoparticles Target Tumors

January 17, 2007

Researchers at Montana State University have used an engineered form of ferritin, a cage-like iron storage protein, to both synthesize and deliver iron oxide nanoparticles to tumors. The investigators, led by Trevor Douglas, ...

Recommended for you

Fast computer control for molecular machines

January 19, 2018

Scientists at the Technical University of Munich (TUM) have developed a novel electric propulsion technology for nanorobots. It allows molecular machines to move a hundred thousand times faster than with the biochemical processes ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.