Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

Nanoparticle Co-Delivery of a Membrane-Associated Protein and a Small-Molecule Anticancer Drug Enhanced Therapeutic Efficacy in a Mouse Model

By BiotechDaily International staff writers
Posted on 23 Jan 2014
Image: The structure of the nanoparticle (left) and how the nanoparticles home in on a tumor and shrink it (right) (Photo courtesy of North Carolina State University).
Image: The structure of the nanoparticle (left) and how the nanoparticles home in on a tumor and shrink it (right) (Photo courtesy of North Carolina State University).
Combining two anticancer drugs within a novel targeted nanoparticle overcomes their shortcomings and forms the basis for a new therapeutic agent with improved inhibition of tumor growth in a mouse xenograft- tumor model.

A team of investigators at North Carolina State University (Raleigh, USA) and the University of North Carolina (Chapel Hill, USA) sought to improve the performance of the cancer drugs doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Although in use for more than 40 years as a primary chemotherapy drug, Dox is known to cause serious heart problems. To prevent these, doctors may limit the amount of Dox given to each patient so that the total amount a patient receives over her or his entire lifetime is 550 milligrams per square meter, or less. Furthermore, the necessity to stop treatment to protect the patient from heart disease may diminish the usefulness of Dox in treating cancer. TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells by binding to certain death receptors. Since the mid-1990s, it has been used as the basis for several anticancer drugs, but has not been found to have any significant survival benefit.

To optimize the action of the two drugs, the investigators created a core and shell-based “nanodepot” consisting of a liposomal core and a crosslinked hyaluronic acid (HA)-based gel shell (designated Gelipo). Since it is a small-molecule drug intercalating the nuclear DNA, Dox was loaded in the aqueous core of the liposome. TRAIL, which acts on the death receptor (DR) on the plasma membrane, was encapsulated in the outer HA shell.

Following injection of the nanoparticles into mice carrying the MDA-MB-231 xenograft tumor, the HA shell was degraded by the hyaluronidase (HAase) enzyme that was concentrated in the tumor environment. This resulted in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes, which caused release of Dox within the tumor cells.

Results published in the January 2, 2014, online edition of the journal Advanced Functional Materials revealed that the parallel activity of TRAIL and Dox showed synergistic anticancer efficacy, with the Dox-TRAIL nanoparticles being 5.9 times more effective than nanoparticles loaded only with Dox.

“In testing on laboratory mice, our technique resulted in significant improvement in breast cancer tumor reduction as compared to conventional treatment techniques,” said senior author Dr. Zhen Gu, assistant professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina.
“Cancer cells can develop resistance to chemotherapy drugs, but are less likely to develop resistance when multiple drugs are delivered simultaneously. However, different drugs target different parts of the cancer cell. For example, the protein drug TRAIL is most effective against the cell membrane, while doxorubicin (Dox) is most effective when delivered to the nucleus. We have come up with a sequential and site-specific delivery technique that first delivers TRAIL to cancer cell membranes and then penetrates the membrane to deliver Dox to the nucleus.”

“This research is our first proof of concept, and we will continue to optimize the technique to make it even more efficient,” said Dr. Gu. “The early results are very promising, and we think this could be scaled up for large-scale manufacturing.”

Related Links:

North Carolina State University
University of North Carolina



comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Alternative splicing produces two protein isoforms (Photo courtesy of Wikimedia Commons).

Key Regulator of Cancer-Inducing Alternative Splicing Identified

Cancer researchers have identified the splicing factor RBM4 (RNA-binding protein 4) as a key determinant in processes that prevent tumor development and spread. RBM4 is known to be crucial to gene splicing... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.