Graphene "carpet planes" fly to cancer cells
Nanonews Network based on materials from North Carolina State University:
‘Flying Carpet’ Technique Uses Graphene to Deliver One-Two Punch of Anticancer Drugs
A new method of drug delivery has been developed by an international team of scientists from North Carolina State University, the University of North Carolina at Chapel Hill and China Pharmaceutical University. As a means of transport – "carpet planes" - for the sequential delivery of two anticancer drugs to cancer cells, the researchers used graphene strips.
Scientists have linked two drugs – TRAIL and DOX – with strips of graphene.
Since TRAIL is most effective when delivered to the outer membrane of a cancer cell, and Dox is most effective when delivered to the nucleus,
the researchers wanted to achieve consistent drug delivery there,
where they will cause the most damage to the cell. (Photo: Zhen Gu)
An international group of scientists has developed a new method of drug delivery, in which graphene strips are used as a means of transport – "carpet planes" - for the sequential transfer of two antitumor drugs to cancer cells. These drugs target different parts of the cell in which they are most effective. The tandem of drugs works better than any of them used as monotherapy, which has been confirmed in experiments on mice with human lung cancer.
In addition, scientists have found that the antitumor protein, TRAIL, can serve as an active molecule that provides binding to the surface of cancer cells, which has not been demonstrated before.
In this study, scientists linked two drugs – TRAIL and doxorubicin (DOX) – to graphene strips. Graphene is a two-dimensional layer of carbon with a thickness of only one atom. Since TRAIL is most effective at delivering to the outer membrane of a cancer cell, and Dox is most effective at delivering to its nucleus, the researchers wanted to achieve consistent delivery of drugs exactly where they will cause the greatest damage to the cell.
Dox physically binds to graphene due to the similarity of the molecular structure of this drug and graphene, and the TRAIL protein is a chain of amino acids, that is, a peptide.
"These drug-enriched graphene strips are injected into the blood in solution and then distributed with the blood as nanoscale flying carpets," explains senior author of an article on the development published in the journal Advanced Materials, Dr. Zhen Gu – Furin-Mediated Sequential Delivery of Anticancer Cytokine and Small-Molecule Drug Shuttled by Graphene.
The mechanism of action of "flying carpets" is based on the phenomenon of increased permeability of blood vessels feeding cancerous tumors. Increased vascular permeability and ensures active penetration of drugs into the tumor.
When the magic carpet comes into contact with a cancer cell, receptors on the cell surface bind to the TRAIL protein, after which enzymes on the cell surface destroy peptides that bind the TRAIL to graphene. This allows the cell to absorb the graphene loaded with doxorubicin and leaves a TRAIL on the surface where it initiates the cell death process.
After the magic carpet is "swallowed" by the cell, the acidic environment inside the cell separates Dox from graphene and gives it the opportunity to attack the nucleus.
The graphene-based nanosystem mediated by furin protease is designed for simultaneous delivery of the membrane-associated cytokine TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) (associated with tumor necrosis factor apoptosis-inducing ligand) and the low-molecular-weight drug doxorubicin (DOX) acting inside the cell. TRAIL and DOX are sequentially released at the plasma membrane and nucleus, respectively. (Fig. Advanced Materials)
"We have shown that TRAIL itself can be used to bind a drug delivery system to a cancer cell, without using an intermediate. This is something we didn't know," says Dr. Gu. "And since graphene has a large surface area, this method increases the efficiency of TRAIL delivery to its target on cancer cell membranes."
The researchers tested their magic carpet method for drug delivery in preclinical trials on human lung cancers (cell line A549) transplanted into laboratory mice. It turned out to be significantly more effective than Dox or TRAIL monotherapy, or a combination of Dox and TRAIL, in which the peptide bond between graphene and TRAIL is not destroyed.
Now scientists are looking for funding to conduct additional preclinical studies to improve their method.
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