A new drug delivery method may enable cancer drugs to overcome resistance mechanisms in tumors, resulting in the destruction of cancer cells using 50 times less chemotherapy than is currently required. The technique, which was developed by researchers from the University of North Carolina at Chapel Hill, has been described as an “invisibility cloak,” allowing medications to reach cancer cells without being detected and destroyed by the body’s own immune system.
Furthermore, the new approach may allow drugs to avoid being ejected from cancer cells once they reach the tumor, thereby providing a solution to the mechanisms that sometimes lead to these cells becoming drug resistant.
Publishing their findings in the journal Nanomedicine: Nanotechnology, Biology and Medicine, the researchers describe how they used exosomes as a vehicle for the delivery of a cancer drug called Paclitaxel. Exosomes are small membrane-bound structures, or vesicles, that are secreted by most cell types. They act as intercellular messengers, carrying proteins, lipids, and genetic material from one cell to another.
The team placed the drug inside exosomes derived from white blood cells, which were then injected into mice with drug-resistant lung cancer. Among other things, they wanted to observe if this delivery method would outperform current techniques that use vesicles made of plastic-based nanoparticles to transport medicine, but which are often identified as foreign by the recipient’s immune system and consequently destroyed.
Because exosomes originate within the body, they were not flagged as a threat by the mice’s immune systems, and were therefore allowed to reach their target. In this regard, the exosomes acted as a kind of “invisibility cloak” for the medication, enabling it to avoid detection once inside the body.
By injecting the exosomes with a dye, the researchers were able to track the vesicles’ movement through the mice, and found that they “possess an extraordinary ability to interact with and accumulate in target cancer cells.” One possible explanation for this is that exosomes are better at fusing with target cells under acidic conditions, and were therefore taken up more readily by the cancer cells than the surrounding tissue, since tumors have an “acidic microenvironment.”
Additionally, the study authors found that the excellent ability of exosomes to fuse with the membranes of cancerous cells ensured that they were not ejected from these cells. Often, cancer drugs are prevented from accumulating in target cells by a process called Pgp-mediated efflux, whereby a transporter protein called P-glycoprotein (Pgp) carries the medicine back across the membrane and out of the cell. It is because of this that some cancers become drug resistant.
Yet by delivering the drug using exosomes, the team was able to bypass this mechanism, ensuring that the contents of these vesicles reached the nucleus of the cancer cells. Subsequently, they found that the medication became 50 times more effective at destroying these cells, meaning that if these results can be replicated in humans, it may be possible to treat drug-resistant lung cancer with 50 times less chemotherapy than is currently necessary.