Navigation Links
Fatty spheres loaded with siRNA shrink ovarian cancer tumors in preclinical trial

A molecular "off" switch packaged in a tiny sphere penetrates deeply into ovarian cancer tumor cells, stifling a troublesome protein and drastically reducing the size of tumors, researchers at The University of Texas M. D. Anderson Cancer Center report in the Aug. 15 edition of Clinical Cancer Research.

The mouse model experiment, featured on the cover of the journal, demonstrates a potent delivery system for short interfering RNA (siRNA) to attack cancer, says senior author Anil Sood, M.D., associate professor in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson.

"Short interfering RNA is a great technology we can use to silence genes, shutting down production of harmful proteins," Sood says. "It works well in the lab, but the question has been how to get it into tumors." Short pieces of RNA don't make it to a tumor without being injected directly, and injection methods used in the lab are not practical for clinical use.

The research team took siRNA that targets a protein that helps ovarian cancer cells survive and spread and rolled it into a liposome -- a lipid ball so small that its dimensions are measured in nanometers (billionths of a meter).

Getting the siRNA inside tumor cells is important, Sood said, because the targeted protein, focal adhesion kinase (FAK), is inside the cell, rather than on the cell surface where most proteins targeted by cancer drugs are found. "Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor," Sood said.

Mice infected with three human ovarian cancer cell lines derived from women with advanced cancer were treated for 3-5 weeks. They received liposomes that contained either the FAK siRNA, a control siRNA, or were empty. Some mice received siRNA liposomes plus the chemotherapy docetaxel.

Mice receiving the FAK-silencing liposome had reductions in mean tumor weight ranging from 44 to 72 percent compared with mice in the control groups. Combining the FAK-silencing liposome with docetaxel boosted tumor weight reduction to the 94-98 percent range.

These results also held up in experiments with ovarian cancer cell lines resistant to docetaxel and to the chemotherapy drug cisplatin.

The FAK-silencing liposome and the liposome with chemotherapy also reduced the incidence of cancer by between 20 and 50 percent in all tested cancer lines.

In addition to its anti-tumor effect, the researchers found that the therapeutic liposome attacked the tumor's blood supply, especially when combined with chemotherapy. By inducing cell suicide (apoptosis) among blood vessel cells, the treatment steeply reduced the number of small blood vessels feeding the tumor, cut the percentage of proliferating tumor cells and increased cell suicide among cancer cells.

Sood and Professor of Molecular Therapeutics Gabriel Lopez-Berestein, M.D., an expert in liposomal therapeutics, cite at least two factors for the success of the anti-FAK liposome.

"This particle is so small, it has no problem getting through the tumor's vasculature and into the tumor," Lopez-Berestein says. The FAK-targeting liposome ranges between 65 and 125 nanometers in diameter. Blood vessels that serve tumors are more porous than normal blood vessels, with pores of 100 to 780 nanometers wide. Normal blood vessel pores are 2 nanometers or less in diameter.

Second, the liposome -- a commercially available version known as DOPC -- has no electrical charge. Its neutrality provides an advantage over positively or negatively charged liposomes when it comes to binding with and penetrating cells.

The next step for the FAK siRNA-DOPC liposome is toxicity testing. "So far it appears to be very well-tolerated," Sood says. "We hope to develop this approach for clinical use in the future."

In addition to ovarian cancer, FAK is overexpressed in colon, breast, thyroid, and head and neck cancers.


'"/>

Source:University of Texas M. D. Anderson Cancer Center


Related biology news :

1. Fatty fish protects against cancer
2. Nanospheres that block pain of sensitive teeth
3. Engineer ramps up protein production, develops versatile viral spheres
4. Penn researchers show how nanocylinders deliver medicine better than nanospheres
5. Biodegradable microspheres deliver time release vaccines, stimulate different immune response
6. MWG Biotech expands siMAX?siRNA portfolio with new scales, lengths and design tools
7. Mice brains shrink during winter, impairing some learning and memory
8. Investigating brain shrinkage in alcoholics
9. Ultrasounds show mothers drinking shrinks fetal brain
10. Bird brains shrink from exposure to contaminants
11. Overfishing large sharks impacts entire marine ecosystem, shrinks shellfish supply
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/24/2017)... Janice Kephart , former 9/11 ... Partners, LLP (IdSP) , today issues the following ... March 6, 2017 Executive Order: Protecting the ... be instilled with greater confidence, enabling the reactivation ... applications are suspended by until at least July ...
(Date:4/13/2017)... 2017 According to a new market research report ... Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, Vertical, and Region ... expected to grow from USD 14.30 Billion in 2017 to USD 31.75 ... ... MarketsandMarkets Logo ...
(Date:4/6/2017)... LONDON , April 6, 2017 ... Control, RFID, ANPR, Document Readers, by End-Use (Transportation & ... Energy Facility, Oil, Gas & Fossil Generation Facility, Nuclear ... Healthcare, Educational, Other) Are you looking for ... Authentication sector? ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... ... 10, 2017 , ... For the second time in three ... Mentoring Award. Representatives of the FirstHand program travelled to Washington, D.C. Tuesday, October ... US2020’s mission is to change the trajectory of STEM education in America by ...
(Date:10/10/2017)... ... 2017 , ... The Pittcon Program Committee is pleased to ... who have made outstanding contributions to analytical chemistry and applied spectroscopy. Each award ... conference and exposition for laboratory science, which will be held February 26-March 1, ...
(Date:10/9/2017)... ... October 09, 2017 , ... ... 5, 2017, in the medical journal, Epilepsia, Brain Sentinel’s SPEAC® System which ... video EEG, in detecting generalized tonic-clonic seizures (GTCS) using surface electromyography (sEMG). ...
(Date:10/6/2017)... , ... October 06, 2017 , ... ... a lunch discussion and webinar on INSIGhT, the first-ever adaptive clinical trial for ... Dana-Farber Cancer Institute. The event is free and open to the public, but ...
Breaking Biology Technology: