Navigation Links
Cholesterol rafts deliver drugs inside cancer cells
Date:4/2/2013

DNA, siRNA and miRNA can reprogram cancer cells that is, if these nucleic acids could cross through the cell membrane. A University of Colorado Cancer Center study published today in the journal Therapeutic Delivery shows that cholesterol "rafts" can shepherd genetic payloads into cancer cells.

"There are many promising therapeutic applications for nucleic acids, but because they can't diffuse across cell membranes on their own, delivery to cancer cells has been a major challenge. Our method is a promising way to get these drugs inside cancer cells where they can do their work," says Tom Anchordoquy, PhD, investigator at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

The technology works by exploiting a relatively new understanding of what cell membranes look like.

"It used to be that we thought about membrane proteins floating around in a disorganized two-dimensional soup. Now we know that different functions are clustered into domains we call rafts," Anchordoquy says. Imagine these rafts like continents of the Earth, each presenting its own plant species. Perhaps a raft with palm trees but not spruce unlocks passage into a cancer cell?

Anchordoquy and colleagues aren't the first to imagine particle-payload delivery systems, but when you engineer and introduce a non-rafted particle into the blood, it quickly becomes coated with all sorts of blood proteins that can cover the membrane proteins ("palm trees") needed to unlock passage into cancer cells. However, blood proteins don't bind to rafts and so particles with rafts continue to present the engineered bits rather than being silted over by the body's proteins. Anchordoquy and colleagues make these rafts by boosting the concentration of cholesterol while forming particles for drug delivery.

"See, rafts are made of 30-50 percent cholesterol, about five times the level in the surrounding lipid. We'd shown in earlier experiments that rafts create more delivery of payload materials into cancer cells, but there was always the outside chance that the benefit was due simply to higher levels of cholesterol and not to the action of the rafts, themselves," Anchordoquy says.

The current study found an elegant fix: with longer tails on lipid molecules, particles will form rafts at lower cholesterol concentrations. The team used long-tailed lipids to form their particles, allowing them to keep cholesterol concentration low while showing the same benefit in delivering genes into cancer cells. This demonstrates that it is indeed the raft that facilitates delivery.

"We've used these synthetic rafts to deliver a gene inside these cells that makes the cells fluoresce," Anchordoquy says. "That way we can see how much payload went in. But because we're talking particles and not just individual molecules, in the future we can send other cargo like microRNA's that can reprogram a cell's gene expression."

Anchordoquy is working with colleagues at the CU Cancer Center to match his delivery system with a potent payload, and welcomes collaboration outside the center as well.


'/>"/>
Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related biology news :

1. Researchers find alternative cholesterol-lowering drug for patients who cant tolerate statins
2. Study identifies liver gene that regulates cholesterol and fat blood levels
3. Cholesterol helps regulate key signaling proteins in the cell
4. Host cholesterol secretion likely to influence gut microbiota
5. Vitamin D supplements do not improve cholesterol as previous research suggested
6. Zebrafish research shows how dietary fat regulates cholesterol absorption
7. Some HDL, or good cholesterol, may not protect against heart disease
8. Study finds cancer-fighting goodness in cholesterol
9. Life span of ovarian grafts longer than expected
10. Drug delivery strategy eliminates myotonia symptoms in mice with myotonic dystrophy
11. Centre for Carbon Measurement set to deliver large carbon reductions
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: