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: Chemists design nanoparticles that can deliver three cancer drugs at a time

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

User comments : 0

More news stories

Shiny quantum dots brighten future of solar cells

(Phys.org) —A house window that doubles as a solar panel could be on the horizon, thanks to recent quantum-dot work by Los Alamos National Laboratory researchers in collaboration with scientists from University ...

Polymer microparticles could help verify goods

Some 2 to 5 percent of all international trade involves counterfeit goods, according to a 2013 United Nations report. These illicit products—which include electronics, automotive and aircraft parts, pharmaceuticals, ...

Patent talk: Google sharpens contact lens vision

(Phys.org) —A report from Patent Bolt brings us one step closer to what Google may have in mind in developing smart contact lenses. According to the discussion Google is interested in the concept of contact ...

Wireless industry makes anti-theft commitment

A trade group for wireless providers said Tuesday that the biggest mobile device manufacturers and carriers will soon put anti-theft tools on the gadgets to try to deter rampant smartphone theft.