Destroy cancer cells: silicon nanoparticles are more effective than liposomes

Medicine and nanotechnology against cancer: "protocells" deliver therapeutic and diagnostic tools to the nucleus of a cancer cell
NanoNewsNet based on Sandia Labs: Sandia and UNM lead effort to destroy cancers

Combining nanotechnological methods with the results of medical research, scientists at the Sandia National Laboratories, the University of New Mexico (UNM), and the Cancer Research and Treatment Center (CRTC) at UNM have developed an effective strategy for using nanoparticles to destroy cancer cells.

In the article The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers, announced on the cover of the May issue of the journal Nature Materials, scientists describe silicon nanoparticles about 150 nanometers in diameter, resembling honeycombs, the cavities of which can be filled with large quantities of various drugs.

"The huge potential of the nanoporous core, with its large surface area, combined with improved targeting of the encapsulating lipid bilayer [liposome] allows a separate "protocell" loaded with a cocktail of drugs to kill resistant cancer cells," comments the essence of the work of its head, Professor Jeff Brinker of the University of New Mexico (Jeff Brinker), a researcher an employee of the Sandia laboratory.

Image of the protocell (cryogenic TEM)
with nanoporous core and lipid
the bilayer is about 4 nm thick.
(Photo: nature.com )

Nanoparticles and the surrounding membranes formed from liposomes, which are practically similar to cellular ones, together make up a combination that can be considered as a "protocell": the membrane "seals" the deadly cargo and is modified by molecules (peptides) specifically binding to receptors overexpressed on the surface of cancer cells. (Too many receptors is one of the signals that the cell is cancerous). Nanoparticles ensure the stability of the membrane and contain therapeutic (or diagnostic, for example, quantum dots) cargo, releasing it inside the cell.

Today, the strategy approved by the U.S. Food and Drug Administration for the delivery of therapeutic drugs using nanoparticles is the use of liposomes. Comparison of target liposomes and protocells with identical membranes and peptide compositions showed that the ability to deliver a larger number of drugs, the stability and effectiveness of targeting protocells lead to a multiple increase in cytotoxicity specifically directed at human liver cancer cells.

Another advantage of protocells over liposomes, says the study's lead author Carlee Ashley, is that using liposomes as a carrier requires specialized loading strategies, which makes the process of their production more complex. Unlike conventional liposomes, nanoporous silicon particles practically simply absorb drugs, being loaded with unique combinations necessary for personalized medicine. In addition to chemotherapeutic drugs, they effectively encapsulate toxins and small interfering RNAs (siRNAs) that suppress gene expression.

Schematic representation of the binding of protocells to the cell membrane using target peptides (1),
internalization of protocells by receptor-mediated endocytosis (2)
and the subsequent release of their cargo in the cytoplasm (3) and nucleus (4) of the cell.
(Fig. nature.com )

RNA, biological messengers that "tell" cells which proteins they should synthesize, in this case are used to suppress synthesis – one of the ways to cause programmed cell death, or apoptosis.

The lipids that make up the membrane serve as a shield limiting the leakage of toxic chemotherapeutic drugs from nanoparticles until they penetrate into the cancer cell. This means that a smaller amount of poison will enter the patient's body if the protocells do not find cancer cells. This coating mitigates the toxic side effects that are almost inevitable during traditional chemotherapy.

Instead, the particles – small enough to remain unnoticed by the "radars" of the liver and other organs – can circulate in the blood for many days or even weeks, depending on their size, looking for their prey and not harming the body.

Using data from the library of phages created in the CRTC – viruses that infect bacteria – scientists have found peptides that specifically bind only to cancer cells.

"Proteins modified with a target peptide binding to cells of a certain carcinoma demonstrate 10,000 times more affinity to these cancer cells than to any other cells of the body," explains Ashley. "The key feature of our protocell is that its liquid bilayer allows high affinity binding to just a few of these peptides. This reduces the likelihood of nonspecific binding and the development of an immune reaction."

The image on the left (Hep3B) shows a fluorescent green liver cancer cell with protocells in it.
Small red dots are lipid bilayer "packages". Their cargo is drug–filled nanoparticles –
penetrates into the cancer cell. Here their pores are filled with a white fluorescent dye for the purpose of visualization.
The penetration is more clearly visible in the second image.
In the picture on the right: protocells do not penetrate into a healthy liver cell (hepatocyte).
(Photo by Carlee Ashley)

Scientists continue to optimize the size of porous silicon nanoparticles obtained by aerosolization of the precursor solution. The process developed by Brinker's laboratory for the production of porous nanoparticles – called evaporation–induced self-assembly - makes it possible to obtain particles from 50 nanometers to several microns in diameter. Particles ranging in size from 50 to 150 nm are ideal for the longest possible circulation in the blood and absorption by cancer cells, so they are pre-selected by size before becoming protocells.

Now the method is being tested on human cancer cells in vivo, and in the near future scientists will start testing it on mouse tumors. According to their estimates, it can become commercially available within five years.