APPLICATIONS OF TECHNOLOGY:
- Targeted drug delivery
- Gene therapy
- Vaccine development
- Imaging agents
- Cancer research
- Long lasting – in vivo half-life 29.5 hours
- Tunable size and stability provide platform for drug formulation
- Low “cargo” leakage
- Deep penetration in tumor tissues – micelles in ~ 15nm range
- Efficient clearance
- Room temperature long-term storage
Ting Xu and her team of Berkeley Lab researchers have developed a potent new vehicle for efficient delivery of small molecule drugs, encapsulating the active ingredients in micelles — spherical nanoparticles only 15 nanometers in diameter. Micelles are vanishingly small soap-like structures that can deliver pharmaceutical agents directly to a target site in the body. Within a day or two, enzymatic activity within the site degrades the peptide structure of the micelles, and their biologically active cargo is unleashed.
The Berkeley Lab micelles have been engineered to last several days within the body before they degrade harmlessly. The spherical skin of these particles is composed of springy, triple-helix polymers, which stabilize the structure. That stability makes these carriers long lasting and less likely to leak their cargoes before they reach their intended target – minimizing the potential collateral damage to healthy cells.
The triple-helix polymers that impart such stability to these micelles are made of amphiphilic peptides, small protein chains that attract water at one end, and attract fatty molecules at the other. These dual and opposing electrochemical properties cause the peptides naturally to form bundles of three, and these “3-Helix” structures in turn self-assemble into hollow spheres, with an outer surface that repels water and an inner surface that surrounds an active molecular ingredient. The spring-like quality of the triple-helices is strengthened by the addition of engineered polyethyelene glycol (PEG) molecules. Such PEGylation enhances the structural stability of the micelles, and helps to maneuver the micelles from the body’s reticular endothelial system, which otherwise may lead to side effects.
Because of their enormous potential for drug delivery systems, micelles are the subject of intensive research. Yet short micelle lifespan, inability to penetrate dense tumors, and inefficient clearance of the breakdown products of micelles have been significant hurdles. The Berkeley Lab micelles overcome these limitations through the triple-helix design, which can be modified to tailor micelles to last a specific time or assume a specific size. This tunable nature underscores the versatility of the triple-helix architecture, making these micelles not one-off designs for drug delivery, but a mobile platform that can be adjusted to deliver a range of molecular cargoes.
Applications for such a platform include highly specific targeting for chemotherapy agents; stealth delivery of anti-inflammatory molecules to sites swarming with antibodies and cytotoxic blood cells; vaccine formulation; and even the precise delivery of DNA for gene therapy. Because of their exquisitely small size and long-lasting nature, these amphiphilic micelle nanoparticles might also be employed as carriers of medical imaging agents to parts of the body inaccessible to larger molecular tags.
DEVELOPMENT STAGE: Bench-scale prototype.
STATUS: Available for licensing or collaborative research.
IB-2813: Issued U.S. Patent 9044514 available at uspto.gov.
IB-3230: Published PCT Patent Applications, Pub. No. WO/2013/155152 and WO/2015/042252 available at wipo.int.
FOR MORE INFORMATION:
Dong, H., Dube, N., Shu, J.Y., Seo, J.W., Mahakian, L.M., Ferrara, K.W., Xu, T., “Long-Circulating 15nm Micelles Based on Amphiphilic 3-Helix Peptide-PEG Conjugates,” ACS Nano, Vol. 6, No. 6, pp. 5320–5329, 2012.
Dong, H., Shu, J.Y., Dube, N., Ma, Y., Tirrell, M.V., Downing, K.H., Seo, J.W., Xu, T., “3-Helix Micelles Stabilized by Polymer Springs,” Journal of the American Chemical Society, Published on Web June 25, 2012.
SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:
REFERENCE NUMBER: JIB-2813, JIB-3230