Nanoporous Particles Deliver Novel Molecular Therapies to Tumors

May 26, 2010

( -- Using nanoporous silicon particles, two teams of investigators have created drug delivery vehicles capable of ferrying labile molecular therapies deep into the body. Both groups believe their new drug delivery vehicles create new opportunities for developing innovative anticancer therapies.

Mauro Ferrari, of the University of Texas Health Sciences Center at Houston, led a research team aiming to develop new methods of delivering therapeutic small interfering RNA (siRNA) molecules to tumors. He and his colleagues published their results of their studies in the journal Cancer Research. Karl Erik Hellstrom, of the University of Washington, and Jun Liu and Chenghong Lei, both of the Pacific Northwest National Laboratory (PNNL), led the research group developing methods for delivering to tumors. Their research was published in the . Dr. Ferrari is the principal investigator of one of the National Cancer Institute’s (NCI) Physical Sciences in Oncology Centers, and he played a seminal role in establishing the NCI’s Alliance for Nanotechnology in Cancer.

siRNA is promising approach to anticancer therapy, and one anticancer siRNA molecule is now in clinical trials in humans (click here for a recent story). However, siRNA molecules are rapidly degraded in the body, so delivering them to tumors requires help.

Dr. Ferrari’s team approached this problem by first encapsulating siRNA molecules in lipid-based nanoparticles. Earlier work by his team had already demonstrated that these lipid nanoparticles could deliver siRNA molecules to tumors, but achieving a therapeutic effect in tumor-bearing mice required twice-weekly injections for many weeks. To reduce the number of injections needed, Dr. Ferrari and his colleagues decided to load their nanoparticle-siRNA construct into the pores of biocompatible nanoporous silicon particles.They then injected their drug delivery vehicle into mice with human ovarian tumors.

When the researchers examined the mice three weeks later, the researchers found that tumors had shrunken markedly and that the siRNA agent was still exerting its biological effect. The investigators also found that toxicities were minimal or non-existent.

Meanwhile, the University of Washington-PNNL team used nanoporous silicon to entrap large numbers of that target a specific tumor-associated protein known as CTLA-4. Monoclonal antibodies targeting CTLA-4 have been shown to produce marked antitumor effects in human clinical trials, but therapeutic levels of this antibody can trigger unwanted autoimmune reactions and other severe side effects. Drs. Hellstrom, Liu, and Lei and their collaborators reasoned that nanoporous silicon particles could act as a reservoir that would maintain therapeutic levels of antibody right at the tumor site while reducing the overall amount of antibody circulating freely in the body.

To test their hypothesis, the investigators injected their construct directly into melanomas growing in mice. As a control, a second set of mice received CTLA-4 monoclonal antibodies injected into the peritoneal cavity. Results of this experiment showed that CTLA-4 monoclonal antibodies delivered using nanoporous silicon produced a month-long suppression of tumor growth with no toxicity, while CTLA-4 antibodies alone had little effect on tumor growth. The first group of animals also lived far longer than the second group.

This work on siRNA is detailed in a paper titled, “Sustained Delivery by Mesoporous Silicon Particles.” Investigators from the University of Texas M.D. Anderson Cancer Center, Rice University, Baylor College of Medicine, University of Texas at Austin, and the University of Puerto Rico Comprehensive Cancer Center also participated in this study. An abstract of this paper is available at the journal’s Web site.

This work with antibodies is detailed in a paper titled, “Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy.” An abstract of this paper is available at the journal’s Web site.

Explore further: Targeted nanoparticles incorporating siRNA offer promise for cancer treatment

Related Stories

Magnetic Nanoworms and Nanocrystals Deliver siRNA to Tumors

September 23, 2009

( -- Small pieces of nucleic acid known as short interfering RNAs, or siRNAs, can turn off the production of specific proteins, a property that makes them one of the more promising new classes of anticancer drugs ...

Pack 'Em In -- Gold Nanoparticles Improve Gene Regulation

February 23, 2009

Investigators at Northwestern University have found that packing small interfering RNA (siRNA) molecules onto the surface of a gold nanoparticle can protect siRNAs from degradation and increase their ability to regulate genes ...

Two-In-One Punch Knocks Out Drug Resistant Cancer Cells

November 4, 2009

( -- Cancer cells, like bacteria, can develop resistance to drug therapy, leading to relapse of disease. One approach showing promise in overcoming multidrug resistance in tumors is to combine two different anticancer ...

Recommended for you

Taming 'wild' electrons in graphene

October 23, 2017

Graphene - a one-atom-thick layer of the stuff in pencils - is a better conductor than copper and is very promising for electronic devices, but with one catch: Electrons that move through it can't be stopped.

Breakthrough in ultra-fast data processing at nanoscale

October 20, 2017

A research team from the National University of Singapore has recently invented a novel "converter" that can harness the speed and small size of plasmons for high frequency data processing and transmission in nanoelectronics.

Art advancing science at the nanoscale

October 18, 2017

Like many other scientists, Don Ingber, M.D., Ph.D., the Founding Director of the Wyss Institute, is concerned that non-scientists have become skeptical and even fearful of his field at a time when technology can offer solutions ...


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.