Nav: Home

Developing a modular, nanoparticle drug delivery system

October 05, 2007

There are two aspects to creating an effective drug: finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job.

With the support from a $478,000, five-year CAREER award from the National Science Foundation, Eva Harth is tackling the second part of this problem. She is creating a modular, multi-functional drug delivery system that promises simultaneously to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs.

(NSF's Faculty Early Career Development awards are the agency's most prestigious honor for junior faculty members and are given to individuals judged most likely to become the academic leaders of the 21st century.)

Harth, who is an assistant professor of chemistry at Vanderbilt University, has created a "nanosponge" specially designed to carry large numbers of drug molecules. She has also discovered a "molecular transporter" that, when attached to the nanosponge, carries it and its cargo across biological barriers into specific intracellular compartments, which are very difficult places for most drugs to reach. She has shown that her system can reach another difficult target: the brain. Experiments have shown that it can pass through the brain-blood barrier. In addition, she has: successfully attached a special "targeting unit" that delivers drugs to the surface of tumors in the lungs, brain and spinal cord and even developed a "light kit" for her delivery system - fluorescent tags that researchers can use to monitor where it goes.

Harth has taken a different approach from other researchers working on nanotechnology for drug development. Instead of trying to encapsulate drugs in nanoscale containers, she decided to create a nanoparticle that had a large number of surface sites where drug molecules could be attached. To do so, she adopted a method that uses extensive internal cross-linking to scrunch a long, linear molecule into a sphere about 10 nanometers in diameter, about the size of a protein. Nanoparticles like this are called nanosponges.

"We can really load this up with a large number of drug molecules," she says.

Working with Heidi Hamm, the Earl W. Sutherland Jr. Professor of Pharmacology at Vanderbilt, Harth synthesized a dendritic molecule with the ability to slip through cell membranes and reach the cell nucleus. They figured out how to attach this "transporter" to her nanoparticle and showed that the transporter can pull the nanoparticle after it into cellular compartments. They also demonstrated that the transporter can deliver large molecules - specifically peptides and proteins - into specific sub-cellular locations.

"Peptides and proteins can act as drugs, just like smaller molecules," Harth says. "However, there is not much activity in this area because people haven't had a method for getting them into cells. Now that there is a way to do it, but that may change."

Hamm studies G proteins, arguably the most important signaling molecules in the cell. Scientists think that many diseases, including diabetes and certain forms of pituitary cancer, are caused by malfunctioning G proteins. She and Harth are collaborating on using the transporter to deliver peptides produced by G proteins that disrupt signaling pathways.

"Eva's methods for drug delivery are very novel and versatile and can be adapted to delivery of proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful," Hamm says.

The chemist is also collaborating with Dennis E. Hallahan, professor of radiation oncology at Vanderbilt, to apply the drug delivery system to fighting cancer. Hallahan's lab had identified a molecule that targets a surface feature on lung carcinomas. Harth took the molecule, improved it, attached it to her nanoparticle and the two of them determined that the combination is capable of delivering drugs to the surface of lung tumors.

She is now working with Hallahan to adapt her delivery system to carry cisplatinum, a traditional chemotherapy agent that is used to treat a number of different kinds of cancer but is highly toxic and has a number of unpleasant side effects.

By delivering the anti-cancer agent directly to the cancerous tissues, Eva's system decreases the adverse effects on other tissues and increases its potency by delivering a higher concentration of the drug directly on the cancer, Hallahan explains.

"The people in my lab have tried at a number of different drug delivery systems and Eva's works the best of those we've looked at," Hallahan says.

Vanderbilt is applying for two patents on the system.
-end-
[Note: A multimedia version of this story is available on the Exploration, Vanderbilt University's online research magazine, at http://www.vanderbilt.edu/exploration/stories/transporter.html.]

Vanderbilt University

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

The Emperor of All Maladies: A Biography of Cancer
by Siddhartha Mukherjee (Author)

Winner of the Pulitzer Prize, and now a documentary from Ken Burns on PBS, The Emperor of All Maladies is a magnificent, profoundly humane “biography” of cancer—from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence.

Physician, researcher, and award-winning science writer, Siddhartha Mukherjee examines cancer with a cellular biologist’s precision, a historian’s perspective, and a biographer’s passion. The result is an astonishingly... View Details


The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

This new and revised edition of the IACP award-winning cookbook brings the healing power of delicious, nutritious foods to those whose hearts and bodies crave a revitalizing meal, through 150 new and updated recipes.

Featuring science-based, nutrient-rich recipes that are easy to prepare and designed to give patients a much-needed boost by stimulating appetite and addressing treatment side effects including fatigue, nausea, dehydration, mouth and throat soreness, tastebud changes, and weight loss. A step-by-step guide helps patients nutritionally prepare for all phases of... View Details


The Truth about Cancer: What You Need to Know about Cancer's History, Treatment, and Prevention
by Ty M Bollinger (Author)

Cancer touches more lives than you may think. According to the World Health Organization, one out of three women alive today, and one out of two men, will face a cancer diagnosis in their lifetime.

To Ty Bollinger, this isn’t just a statistic. It’s personal. After losing seven members of his family to cancer over the course of a decade, Ty set out on a global quest to learn as much as he possibly could about cancer treatments and the medical industry that surrounds the disease. He has written this book to share what he’s uncovered—some of which may shock you—and to give you... View Details


F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

*A portion of the proceeds from this book will be donated to support research dedicated to finding a cure for cancer. Because fuck cancer.

This book is for you.

If you are fighting cancer, this is for you. If your brother, sister, mom, dad, son, daughter, relative, or friend is fighting cancer, this is for you. If you've lost someone to cancer like I have, this is for you. If cancer affects your life in any way, this is for you.

The stress of cancer can feel crushing. But perhaps this book can help you get away from it all, if only for a little... View Details


Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

The revolutionary, New York Times bestselling guide to the powerful lifestyle changes that fight and prevent cancer—an integrative approach based on the latest scientific research
 
“A common-sense blueprint for healthy living.” —Chicago Tribune
 
“Resonating with cancer support communities and recommended nationwide.” —Los Angeles Times
 
“Life affirming . . . filled with practical advice.” —The Seattle Times
 
David Servan-Schreiber was a rising... View Details


Cancer Hates Tea: A Unique Preventive and Transformative Lifestyle Change to Help Crush Cancer
by Maria Uspenski (Author), Dr. Mary L. Hardy (Foreword)

Drink Tea to Tell Cancer ‘Hit the Road’

Become a tea lover with a purpose and help your body defend itself against cancer. Learn to embrace tea in all its varieties― green, white, black, pu-erh, herbal and more―as both a mental and physical experience to protect your health. Discover the history, growing information and health implications of each variety, as well as uniquely delicious methods to boost your intake with serving suggestions, food pairings and recipes that highlight the benefits of tea.

After her own battle with cancer, Maria Uspenski extensively... View Details


Anti-Cancer Smoothies: Healing With Superfoods: 35 Delicious Smoothie Recipes to Fight Cancer, Live Healthy and Boost Your Energy
by Linda H. Harris (Author)

Anti-Cancer Diet, Cancer Fighting Foods, and Cancer Nutrition

Whether you have cancer or you're at risk of cancer because of your family history - the way you eat can have a major impact on your health and your ability to fight or manage your disease. Cancer is notorious for sapping the strength and nutrition out of a person's body. You'll need to replace a lot of the vitamins, nutrients and minerals that certain drugs and treatments deplete.

The Anti-Cancer Smoothies in this book are made of healthy and tasty vegetables, fruits, spices and herbs that are known to fight cancer.... View Details


The Biology of Cancer, 2nd Edition
by Robert A. Weinberg (Author), Robert A Weinberg (Author)

Thoroughly updated and incorporating the most important advances in the fast-growing field of cancer biology, The Biology of Cancer, Second Edition, maintains all of its hallmark features admired by students, instructors, researchers, and clinicians around the world.

The Biology of Cancer is a textbook for students studying the molecular and cellular bases of cancer at the undergraduate, graduate, and medical school levels. The principles of cancer biology are presented in an organized, cogent, and in-depth manner. The clarity of writing, supported by an extensive... View Details


A Cancer Battle Plan: Six Strategies for Beating Cancer, from a Recovered "Hopeless Case"
by Anne E. Frahm (Author), David J. Frahm (Author)

When Anne Frahm discovered she had cancer, it had already spread from her breast to her shoulder, ribs, skull, and pelvic bone, and had eaten into every vertebrae in her spine.Doctors prescribed the traditional treatments of surgery, radiation, and chemotherapy, but Anne continued to sicken. Yet, throughout the course of her disease the author persisted in researching the connection between cancer and nutrition. She formulated a comprehensive battle plan and within five weeks of implementing it, her cancer disappeared without a trace. She has been cancer-free ever since.

As A... View Details


Beating Cancer with Nutrition (Fourth Edition) Rev
by Patrick Quillin (Author)

There is good news in the "war on cancer". Optimal nutrition coupled with appropriate medical treatment can dramatically improve the quality and quantity of life and chances for a complete remission for most cancer patients. A well-nourished cancer patient can better manage the disease. Cancer is the number two cause of death in America and the developed nations of the world with one out of four dying from cancer and 38% of women and 43% of men projected to develop cancer over their lifetime. While the overall death rate from cancer has not appreciably declined since... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Big Five
What are the five biggest global challenges we face right now — and what can we do about them? This hour, TED speakers explore some radical solutions to these enduring problems. Guests include geoengineer Tim Kruger, president of the International Rescue Committee David Miliband, political scientist Ian Bremmer, global data analyst Sarah Menker, and historian Rutger Bregman.
Now Playing: Science for the People

#457 Trowel Blazing
This week we look at some of the lesser known historical figures and current public perception of anthropology, archaeology, and other fields that end in "ology". Rebecca Wragg Sykes, an archaeologist, writer, and co-founder of the TrowelBlazers, tells us about the Raising Horizons project and how their team is trying to shine the spotlight on the forgotten historical women of archaeological, geological, and palaeontological science. And Kristina Killgrove, assistant professor of anthropology at the University of West Florida and science writer, talks about the public perception of the fields of anthropology and archeology, and how those science are represented -...