One of the hardest things about fighting cancer is that drugs often hit healthy cells just as hard as the cancerous cells, causing patients to become sick from the drugs meant to help save them.
As a result researchers constantly search for new ways to increase the safety and efficacy of existing anticancer therapies. Ideally, drugs should target tumor cells while avoiding healthy cells, organs or tissue, and the drug should get to all of the cancer cells within the tumor at doses high enough to kill the cancer cells.
Recent advances in drug delivery and targeted therapies such as targeted nanoparticles have put scientists closer to achieving these goals.
While the concept of targeted drug delivery is not new, the use of nanoparticles to carry drugs directly to tumor cells (nanomedicines) has recently become an intensely studied field.
Nanoparticles are extremely small in size (less than 1 micrometer) and comprised of various compounds used to transport anticancer agents to a given target. One can envision these particles as small molecular packages able to carry drug payloads to tumors. The nanoparticles not only carry the drug or antitumor agents, but they also protect the compounds from degradation and loss during the delivery process.
Because of these properties, nanoparticles allow concentrated delivery of anticancer drugs directly to the tumor site. The first nanoparticles are already being used in the clinic and include particles composed of a protein called albumin and the chemotherapy drug paclitaxel (Abraxane). In addition, nanoparticles known as liposomes have been loaded with the drug doxorubicin (Doxil).
Although these particles can carry chemotherapy drugs to tumors, they are not specifically directed to do so since they do not contain a signal that tells them to only target tumor cells.
One way to increase the specific targeting of nanoparticles to tumor cells is to attach antibodies or a small peptide directly to the nanoparticle surface. The antibodies or peptides act like a homing beacon that binds specifically to a protein that is present in cancer cells, but not in healthy tissues. This approach concentrates the drug to the disease site and limits the exposure of healthy tissues to the cancer drugs, resulting in remarkable increases in drug activity and safety of existing and promising new anticancer therapies.
The final hurdle is getting the anticancer drug to all of the cancer cells within the tumor. All cancer drugs share the same problem when treating solid tumors: they penetrate just a few cells into the tumor as the drugs exit the blood vessels. As a result, they fail to reach a large proportion of cancer cells inside the tumor. This process can also expose some cells to lethal drug concentrations, but leads to sub-optimal drug exposure for others.
This sub-optimal exposure leads to incomplete anticancer activity and allows the cancer cell time to defend itself from the drug and become drug resistant. Recently, researchers have identified and developed tumor-penetrating peptides that increase the distribution of drugs throughout tumors. This approach allows more tumor cells to “see” the drug and at concentrations high enough to cause tumor cell death. How well this approach translates to treatment in people is yet to be determined, but studies examining the idea are being pursued.
By combining targeted drug approaches, nanomedicine and tumor penetrating peptides, researchers now have new tools to target solid tumors and prevent or overcome drug resistance.
Good things may come in small, but highly targeted packages designed specifically for cancer patients may lead to more effective and better-tolerated cancer therapies.