New Nanoparticles Could Lead To End Of Chemotherapy

Nanoparticles specially engineered by University of Central Florida Assistant Professor J. Manuel Perez and his colleagues could someday target and destroy tumors, sparing patients from toxic, whole-body chemotherapies.Perez and his team used a drug called Taxol for their cell culture studies, recently published in the journal Small, because it is one of the most widely used chemotherapeutic drugs. Taxol normally causes many negative side effects because it travels throughout the body and damages healthy tissue as well as cancer cells.

The Taxol-carrying nanoparticles engineered in Perez's laboratory are modified so they carry the drug only to the cancer cells, allowing targeted cancer treatment without harming healthy cells. This is achieved by attaching a vitamin (folic acid) derivative that cancer cells like to consume in high amounts.

Because the nanoparticles also carry a fluorescent dye and an iron oxide magnetic core, their locations within the cells and the body can be seen by optical imaging and magnetic resonance imaging (MRI). That allows a physician to see how the tumor is responding to the treatment.

The nanoparticles also can be engineered without the drug and used as imaging (contrast) agents for cancer. If there is no cancer, the biodegradable nanoparticles will not bind to the tissue and will be eliminated by the liver. The iron oxide core will be utilized as regular iron in the body.

"What's unique about our work is that the nanoparticle has a dual role, as a diagnostic and therapeutic agent in a biodegradable and biocompatible vehicle," Perez said.

Perez has spent the past five years looking at ways nanotechnology can be used to help diagnose, image and treat cancer and infectious diseases. It's part of the quickly evolving world of nanomedicine.

The process works like this. Cancer cells in the tumor connect with the engineered nanoparticles via cell receptors that can be regarded as "doors" or "docking stations." The nanoparticles enter the cell and release their cargo of iron oxide, fluorescent dye and drugs, allowing dual imaging and treatment.

"Although the results from the cell cultures are preliminary, they are very encouraging," Perez said.

A new chemistry called "click chemistry" was utilized to attach the targeting molecule (folic acid) to the nanoparticles. This chemistry allows for the easy and specific attachment of molecules to nanoparticles without unwanted side products. It also allows for the easy attachment of other molecules to nanoparticles to specifically seek out particular tumors and other malignancies.

Perez's study builds on his prior research published in the prestigious journal Angewandte Chemie Int. Ed. His work has been partially funded by a National Institutes of Health grant and a Nanoscience Technology Center start-up fund.

"Our work is an important beginning, because it demonstrates an avenue for using nanotechnology not only to diagnose but also to treat cancer, potentially at an early stage," Perez said.

Perez, a Puerto Rico native, joined UCF in 2005. He works at UCF's NanoScience Technology Center and Chemistry Department and in the Burnett School of Biomedical Sciences in the College of Medicine. He has a Ph.D. from Boston University in Biochemistry and completed postdoctoral training at Massachusetts General Hospital, Harvard Medical School's teaching and research hospital.

Protein May Be Strongest Indicator Of Rare Lung Disease

Researchers at the University of Cincinnati (UC) have discovered a protein in the lungs that can help in determining progression of the rare lung disease Idiopathic Pulmonary Fibrosis (IPF).Researchers say the protein—Serum surfactant protein A—is superior to other IPF predictors and could lead to better decisions about treatment and timing of lung transplantation.

The study, led by Brent Kinder, MD, is published in the June 4 edition of the journal Chest.

Surfactant proteins are lipoproteins that allow the lungs to stretch and function. These have previously been investigated by UC pulmonary researchers Frank McCormack, MD, and Jeffrey Whitsett, MD.

Kinder and colleagues report that Serum surfactant protein A is the strongest predictor of a patient's survival in the first year after diagnosis with IPF.

"A simple blood test may give us the information we need to help determine the short term risk of death in a patient with IPF," says Kinder, an assistant professor of medicine at the UC College of Medicine and pulmonologist with UC Physicians. "This protein is a stronger predictor of the severity of illness than age, symptoms or prognostic data, like breathing tests."

IPF is scarring of the lung. As the disease progresses, air sacs in the lungs become replaced by fibrotic scar tissue. Lung tissue becomes thicker where the scarring forms, causing an irreversible loss of the tissue's ability to carry oxygen into the bloodstream.

IPF is one of about 200 disorders called interstitial lung diseases, which affect the thick tissue of the lung as opposed to more common lung ailments—such as asthma or emphysema—that affect the airways.

IPF is the most common form of interstitial lung diseases and affects about 128,000 people in the United States, with an estimated 48,000 new cases diagnosed each year. There currently are no proven therapies or cures for IPF.

Kinder, director of UC's Interstitial Lung Disease Center, says this new indicator will allow doctors to determine the severity of the disease in a fast, effective manner and will help them decide the best way to go about treating it.

"It will allow us to come to a decision about how or if to treat the IPF patient and get them enrolled in clinical trials immediately," he says. "In severe cases, it can help in scheduling a lung transplant at the most optimal time for the patient.

"Overall, this discovery could help us define the window of opportunity to appropriately try more aggressive therapies and could greatly help improve the lives of those living with IPF."

This study was funded in part by a Support of Continuous Research Excellence (SCORE) grant from the National Institutes of Health and a UC Dean's Scholars award for clinical research.

Swine Flu Origins Revealed

A new analysis of the current swine-origin H1N1 influenza A virus suggests that transmission to humans occurred several months before recognition of the existing outbreak.The work, published online in Nature June 10, highlights the need for systematic surveillance of influenza in swine, and provides evidence that new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans.

'Using computational methods, developed over the last ten years at Oxford, we were able to reconstruct the origins and timescale of this new pandemic,' said Dr Oliver Pybus of Oxford University's Department of Zoology, an author of the paper. 'Our results show that this strain has been circulating among pigs, possibly among multiple continents, for many years prior to its transmission to humans.'

Dr Pybus, along with Andrew Rambaut from the University of Edinburgh and colleagues, used evolutionary analysis to estimate the timescale of the origins and the early development of the epidemic. They believe that it was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak.

The team conclude that 'despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years.'

The team included researchers from Oxford, the University of Edinburgh, the University of Hong Kong and the University of Arizona.