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

Nov 04, 2009

(PhysOrg.com) -- 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 agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. An example of this approach appears in the journal Small.

Huixin He and Tamara Minko led a team of investigators from academia and industry that used porous silica to deliver to a traditional anticancer drug together with a therapeutic (siRNA) molecule. Doxorubicin, the , kills tumors by triggering a form of cell death known as apoptosis, while the siRNA the researchers used suppresses the production of the protein Bcl-2, which produce to stop apoptosis.

To create this two-for-one therapeutic, the investigators first load doxorubicin into the pores of silica nanoparticles and then coat the nanoparticle with spherical polymer nanoparticles known as dendrimers. The dendrimer-coated nanoparticles bind tightly to siRNA molecules, creating the novel therapeutic. When administered to multidrug resistance ovarian cancer cells, the nanoparticle formulation was over 130 times more lethal to the cells than was free doxorubicin. Most of this increase in anticancer activity resulted from the effects of the siRNA therapy.

The researchers noted, however, that since the nanoparticle uptake appears to be endocytosis mediated, and the doxorubicin delivered into the nucleus and perinuclear region of the cell, it is likely that this therapeutic approach is also able to bypass the pump mechanism cancer cells use to remove drugs that enter the cell via diffusion pathways. The researchers also found that the nanoparticles release very little of their doxorubicin payload outside of the cells, suggesting that the nanoparticle-based therapy might reduce the side effects associated with doxorubicin treatment.

This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, "Co-delivery of and Bcl-2 siRNA by Mesoporous Silica Nanoparticles Enhances the Efficacy of Chemotherapy in Multidrug-Resistant Cancer Cells." Investigators from Carl Zeiss SMT and Merck & Co. also participated in this study.

An abstract of this paper is available at the journal's Web site.

Provided by National Cancer Institute (news : web)

Explore further: Research reveals how our bodies keep unwelcome visitors out of cell nuclei

add to favorites email to friend print save as pdf

Related Stories

Double-Duty Nanoparticles Overcome Drug Resistance in Tumors

Jun 14, 2007

Cancer cells, like bacteria, can develop resistance to drug therapy. In fact, research suggests strongly that multidrug resistant cancer cells that remain alive after chemotherapy are responsible for the reappearance of tumors ...

Pack 'Em In -- Gold Nanoparticles Improve Gene Regulation

Feb 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 ...

Nanoparticles Overcome Anticancer Drug Resistance

Jun 12, 2006

Too often, chemotherapy fails to cure cancer because some tumor cells develop resistance to multiple anticancer drugs. In most cases, resistance develops when cancer cells begin expressing a protein, known as p-glycoprotein, ...

Photochemistry Creates Drug-Trapping Nanoparticles

Oct 09, 2006

Many of the most potent anticancer agents are poorly soluble in water, presenting a challenge for medicinal chemists who must develop methods of delivering these drugs in the watery environment of the human body. Nanoparticles ...

Magnetic Nanoworms and Nanocrystals Deliver siRNA to Tumors

Sep 23, 2009

(PhysOrg.com) -- 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 ...

Recommended for you

A gut reaction

Nov 19, 2014

Queen's University biologist Virginia Walker and Queen's SARC Awarded Postdoctoral Fellow Pranab Das have shown nanosilver, which is often added to water purification units, can upset your gut. The discovery ...

User comments : 0

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.