The first figure is an artistic depiction of red blood cells that are eventually turned into the vessels for nanoparticles. The second figure is an actual photo of an RBC-wrapped nanoparticle. | Photo and image courtesy of Dr. Che-Ming Jack Hu.
Robots in Disguise: Nanoparticles as Red Blood Cells
This idea is not the next Transformers, but it might as well be.
For years, scientists have toyed with the concept of using nanotechnology for drug delivery. With little to no side effects, higher rates of patient compliance, and a particular usefulness in cancer therapy–since tumors can be specifically targeted–their ideas are not baseless. The only problem is making the medicine circulate in the bloodstream long enough without the patient’s immune system destroying it, an obstacle that researchers still struggle with today.
The current, most widespread solution to this problem is called polyethylene glycol (PEG) functionalization, where the nanoparticles are wrapped within water so that they are not targeted as often by the immune response. However, despite its success, anti-PEG responses by the patient’s immune system have been recently discovered–meaning that new ways of ensuring the survival of the medicine need to be found.
Inspired by nature, some researchers have focused on creating a red blood cell-like vessel to carry the medicine, but have not come far. Even though red blood cells (RBCs) last 120 days in the body, there have been struggles to create a synthetic RBC membrane. By taking a different approach to this idea, a research team at UC San Diego has succeeded where others have not.
“The conventional trend of thought in creating an immunocompatible nanoparticle is to use very hydrophilic polymers to retain water, thereby hiding particles behind a layer of water,” said Dr. Che-Ming Jack Hu, the lead researcher.
The Department of NanoEngineering at UCSD’s Jacobs School of Engineering has decided to forgo the tedious biological aspects of synthesizing RBC membranes and have instead taken an actual membrane from a real RBC. To separate the membrane from its inner components, the cell is placed in a hypotonic solution where water is forced into the RBC, which then bursts. The proteins inside are separated afterward; these steps are repeated as necessary to purify the membranes, which are wrapped around the nanoparticles later on. This revolutionary approach is seeing great results in the lab, where the nanoparticles wrapped in RBC membranes last twice as long as their PEG-coated counterparts. Even greater benefits are the ease of synthesis and customization ability. Using a patient’s own blood, scientists will be able to create individual drug delivery vessels out of the provided patient blood cells, possibly eliminating the chances of an immune response.
Due to the success of the natural RBC membranes during tests, the focus has shifted to developing a way to transform this method so that it may be manufactured, along with figuring out how to deliver more than one drug at a time.
“What inspires us to use natural RBC membranes is the incredible biochemical complexity in them that serves to provide a “self” signal to the body. Humans’ immune system is excellent at recognizing foreign bodies and clearing them, and currently synthetic efforts fall quite short in recreating a “self” mimicking surface. We therefore decided to exploit natural RBC membranes,” said Dr. Hu. “Our approach in combining natural components with synthetic materials sets a new paradigm in nanoparticle preparation. Such an idea requires multi-disciplinary backgrounds, [an] innovative mindset, and the boldness to defy existing paradigms.”
Reference: Fong, R.H., C.M. Hu, and L. Zhang. (2012). Nanoparticles disguised as red blood cells to evade the immune system. Expert Opinion on Biological Therapy, 12, 385-389.