Featured Research

from universities, journals, and other organizations

Natural plant protein converted into drug-delivery vehicles

Date:
July 3, 2012
Source:
University of Pennsylvania
Summary:
Finding biocompatible carriers that can get drugs to their targets in the body involves significant challenges. Researchers have now shown a new approach for making vesicles and fine-tuning their shapes. By starting with a protein that is found in sunflower seeds, they used genetic engineering to make a variety of protein molecules that assemble into vesicles and other useful structures.

Recombinant technology allowed the researchers to make different variants of the plant protein oleosin.
Credit: Image courtesy of University of Pennsylvania

Finding biocompatible carriers that can get drugs to their targets in the body involves significant challenges. Beyond practical concerns of manufacturing and loading these vehicles, the carriers must work effectively with the drug and be safe to consume. Vesicles, hollow capsules shaped like double-walled bubbles, are ideal candidates, as the body naturally produces similar structures to move chemicals from one place to another. Finding the right molecules to assemble into capsules, however, remains difficult.

Researchers from the University of Pennsylvania have now shown a new approach for making vesicles and fine-tuning their shapes. By starting with a protein that is found in sunflower seeds, they used genetic engineering to make a variety of protein molecules that assemble into vesicles and other useful structures.

Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering, graduate student Kevin Vargo and research scientist Ranganath Parthasarathy of the Department of Chemical and Biomolecular Engineering in Penn's School of Engineering and Applied Science conducted the research.

Their work was published in the Proceedings of the National Academy of Sciences.

"To our knowledge, this is the first time a vesicle has been made from a recombinant protein," Hammer said.

Recombinant proteins are the products of a well-established technique that involves introducing a designed gene sequence into a host organism -- in most cases, the bacterium E. coli -- in order to get that organism to make a protein it would not normally produce.

Hammer's group worked for nearly a decade to find a protein that was biocompatible, could be produced through recombinant methods and, most important, could be induced to form vesicles.

"The molecule we identified is called oleosin," Hammer said. "It's a surfactant protein found in sunflower and sesame seeds."

Surfactants are soap-like chemicals that have two distinct sides; one side is attracted to water and the other is repelled by it. They can make many structures in solution but making vesicles is rare. Most often, surfactants make micelles, in which a single layer of molecules aggregates with the water-loving part on the outside and the water-hating part on the inside. Micelles have a limited ability to carry drugs. Vesicles, in contrast, have two walls aligned so the two water-hating sides face each other. The water-loving interior cavity allows the transport of a large payload of water-soluble molecules that are suspended in water. Since many drugs are water soluble, vesicles offer significant advantages for drug delivery.

The team systematically modified oleosin to find variants of the molecule that could form vesicles. Getting oleosin to take this complex shape meant selectively removing and changing parts of oleosin's gene sequence so that the corresponding protein would fold the way the researchers wanted after it was produced by the E.coli.

"We started by truncating the sequence that codes for the hydrophobic part, shortening the protein itself," Hammer said. "We did more complex truncations at the ends for separation and to control the shape of the assembly."

"There are simple ways to correlate the gene sequence to the geometry you get in the protein," Vargo said. "For example, getting the right amount of curvature to make a spherical vesicle means the chains should be sufficiently large that they do not pack tightly."

In the process of finding the right protein for this task, the researchers came up with several other useful protein variants that form different shapes, including sheets and fibers, when grown in the appropriate salt solutions.

Materials made by recombinant methods offer an additional advantage in that the precise sequence of amino acids can be controlled for targeting to specific receptors and other biological targets. For proteins of this size, this level of control is not attainable by any other method.

"Other groups have synthesized polypeptide vesicles, but they have a hard time controlling the sequences in individual sections of their molecules," Vargo said. "We can go in a change a single amino acid in the protein by modifying the corresponding part of the gene."

"Recombinant methods mean we can make polymers that are all of a defined length and dictate the chemical composition at each location along that length," Hammer said. "You get the exact length and sequence every time."

According to Hammer's team, the hardest part of the research was confirming that these sequences did indeed fold into vesicles. This was only possible with specialized equipment available to the researchers through their association with Penn's Materials Research Science and Engineering Center and made possible by a grant written by professor Karen Winey from Materials Science and Engineering.

"The vast majority of our time in this project was doing the imaging; making the protein was relatively easy," Hammer said.

The imaging technique used is known as cyro-transmission electron microscopy, or cryoTEM

"With cryoTEM," Vargo said, "we create a thin layer of solution, then plunge it into ethane, freezing it fast enough that the water doesn't crystallize. Ice crystals would also destroy the vesicles, so this technique leaves you with your particles and structures intact."

As their protein is already routinely eaten, the researchers are confident that their oleosin vesicles will be of great interest in drug-delivery applications, particularly oral-drug delivery. Future work will entail adding genes for functional groups to allow the vesicles to target certain tissues, as well as determining whether the proteins can be induced to change shape once they reach their targets.

"This research opens up the possibility of using switchable motifs to allow us to release high concentrations of drugs on different cues, such as a change in acidity," Hammer said. "Tumor microenvironments and the interior of tumors are known to be acidic, so a vesicle that falls apart in acidic environments would be extremely valuable."

The work was supported by the National Science Foundation through the Penn MRSEC and the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering.


Story Source:

The above story is based on materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. B. Vargo, R. Parthasarathy, D. A. Hammer. Self-assembly of tunable protein suprastructures from recombinant oleosin. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1205426109

Cite This Page:

University of Pennsylvania. "Natural plant protein converted into drug-delivery vehicles." ScienceDaily. ScienceDaily, 3 July 2012. <www.sciencedaily.com/releases/2012/07/120703200546.htm>.
University of Pennsylvania. (2012, July 3). Natural plant protein converted into drug-delivery vehicles. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2012/07/120703200546.htm
University of Pennsylvania. "Natural plant protein converted into drug-delivery vehicles." ScienceDaily. www.sciencedaily.com/releases/2012/07/120703200546.htm (accessed July 22, 2014).

Share This




More Matter & Energy News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Government Approves East Coast Oil Exploration

Government Approves East Coast Oil Exploration

AP (July 18, 2014) The Obama administration approved the use of sonic cannons to discover deposits under the ocean floor by shooting sound waves 100 times louder than a jet engine through waters shared by endangered whales and turtles. (July 18) Video provided by AP
Powered by NewsLook.com
Sunken German U-Boat Clearly Visible For First Time

Sunken German U-Boat Clearly Visible For First Time

Newsy (July 18, 2014) The wreckage of the German submarine U-166 has become clearly visible for the first time since it was discovered in 2001. Video provided by Newsy
Powered by NewsLook.com
Obama: U.S. Must Have "smartest Airports, Best Power Grid"

Obama: U.S. Must Have "smartest Airports, Best Power Grid"

Reuters - US Online Video (July 17, 2014) President Barak Obama stopped by at a lunch counter in Delaware before making remarks about boosting the nation's infrastructure. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Crude Oil Prices Bounce Back After Falling Below $100 a Barrel

Crude Oil Prices Bounce Back After Falling Below $100 a Barrel

TheStreet (July 16, 2014) Oil Futures are bouncing back after tumbling below $100 a barrel for the first time since May yesterday. Jeff Grossman is the president of BRG Brokerage and trades at the NYMEX. Grossman tells TheStreet the Middle East is always a concern for oil traders. Oil prices were pushed down in recent weeks on Libya increasing its production. Supply disruptions in Iraq fading also contributed to prices falling. News from China's economic front showing a growth for the second quarter also calmed fears on its slowdown. Jeff Grossman talks to TheStreet's Susannah Lee on this and more on the Energy Department's Energy Information Administration (EIA) report. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins