Biodegradable nanoprobe images new blood vessel growth
The generation of new mouse models of human disease is accelerating rapidly due to the completion of whole-genome sequencing efforts and technological advances in the manipulation of the mouse genome. The speed of progress in this endeavour has highlighted the shortage of experts to fully characterise the new mouse lines produced. A European
Full Post: Impending crisis in provision of histopathology expertise for mouse functional genomics
Angiogenesis, the growth of new blood vessels, plays a critical role in several chronic human diseases, including metastatic cancer. In fact, several new anticancer therapies are designed to starve tumors by shutting down angiogenesis, but the lack of a good assay for quantifying angiogenesis in the body has hampered the development of effective antiangiogenesis therapies.
Late fall 2008, researchers at The Siteman Center of Cancer Nanotechnology Excellence described a novel nanoparticle capable of imaging angiogenesis using magnetic resonance imaging (click here to see earlier story). Now, researchers at the University of California, Berkeley, have developed a second type of nanoparticle that can image angiogenesis using positron emission tomography (PET). The investigators, led by Jean Fréchet, Ph.D., describe their new nanoparticle in a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America.
The investigators used a nanoparticle known as a dendrimer, a spherical polymer with multiple chemical functionality built into its structure. This chemical functionality enabled the investigators to incorporate radioactive bromine-76 into the core of the dendrimer and add a targeting agent to the outside of the dendrimer. For a targeting agent, the researchers used cyclic-RGD, a well-studied peptide that binds strongly to the integrin avb3, a protein expressed only on the surface of new blood vessels. The dendrimer itself was designed to degrade in the body once imaging is complete.
Studies using cells grown in culture showed that cells expressing avb3 readily took up the targeted dendrimers, whereas other cells did not. These experiments also showed that binding affinity for the targeted nanoparticle was some fiftyfold higher than for cyclic-RGD alone. This significant boost in binding affinity likely results from a Velcro?-like effect in which multiple cyclic-RGD molecules on the nanoparticle bind simultaneously to multiple avb3 molecules on the surface of target cells. Subsequent studies in mice showed that the targeted dendrimer was able to image sites of angiogenesis with relatively little background from nonspecific binding.
This work is detailed in the paper “Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis.” Investigators from Washington University in St. Louis also participated in this study. An abstract of this paper is available at the journal’s Web site. View abstract
Working with a nanoparticle designed to target and image glioblastoma, a form of brain cancer, investigators at the University of Washington in Seattle have found that these same nanoparticles inhibit tumor cell invasion, one of the key events that leads to the metastatic spread of cancer. The investigators have also determined how the nanoparticles exert
Full Post: Toxin-nanoparticle combo inhibits brain cancer invasion while imaging tumors
One of the key steps in the development of any drug or imaging agent intended for human use is measurement of the adsorption, metabolism, and excretion of the drug. Quantifying this collection of pharmacological properties, known as ADME, is a challenging and time-consuming process that is even more difficult when the drug or imaging
Full Post: Measuring nanoparticle behavior in the body using MRI
Research has shown that a particular receptor for the blood protein thrombin is overexpressed by highly metastatic melanoma cells. When activated, this receptor triggers a wide range of biochemical changes that increase the metastatic activity of melanoma cells. To prevent those biochemical changes from occurring, a team of investigators at The University of Texas
Full Post: Nanoparticle targets melanoma with siRNA
One of the hallmarks of many nanoparticle-based anticancer therapeutics and imaging agents is that they accumulate in tumors thanks to the fact that they are small enough to escape from the bloodstream through the leaky blood vessels that surround tumors. And although many if not most tumors are surrounded by leaky blood vessels, the
Full Post: Nanoparticle reports on drug delivery to breast tumors, predicts response to therapy
A research team from the Massachusetts Institute of Technology (MIT)-Harvard Center for Nanotechnology Excellence has custom-designed nanoparticles that can deliver the anticancer drug cisplatin specifically to prostate cancer cells. The nanoparticles are composed of two different polymers and are decorated with a nucleic acid aptamer that binds to the tumor marker prostate-specific membrane antigen.
Full Post: Targeted nanoparticles boost platinum-based anticancer therapy