In this blog post, we’ll explore how selective drug delivery systems utilizing nanotechnology can reduce the side effects of cancer treatment and improve treatment outcomes.
There’s a proverb that says, “To kill a bedbug, you end up burning down the whole house.” These days, simply spraying insecticide is enough to kill bedbugs, but this proverb still applies—not to houses, but to the human body. If cancer is detected early, it can be treated by surgically removing only the affected area. However, when cancer is detected in the middle or late stages and has already metastasized, the extent of the lesions is extensive and cancer cells have spread to multiple sites, making it practically impossible to surgically remove all affected areas. Therefore, systemic chemotherapy—administering anticancer drugs throughout the body—is performed, and it is precisely during this process that side effects occur. The drugs used in chemotherapy affect not only cancer cells but also healthy cells, causing various side effects such as pain, vomiting, hair loss, and skin damage. It is akin to burning down a thatched-roof cottage to kill bedbugs—in the process of eliminating cancer cells, healthy tissue is damaged as well.
Research aimed at reducing these side effects is proceeding in two main directions. One is the development of anticancer drugs with fewer side effects, and the other is the selective delivery of existing anticancer drugs only to the site of the cancer. Generally, since cancer cells are also cells, it is believed that there are limitations to creating drugs that perfectly target only cancer cells without affecting normal cells at all. Therefore, technologies that concentrate the delivery of anticancer drugs to cancerous tissue are currently receiving greater attention. To achieve this, the drug must be delivered selectively to cancer cells with minimal delivery to normal tissue, and it must be possible to verify that the drug has actually reached the intended location. The technology used to meet these conditions is nanotechnology.
Nanoparticles must possess several characteristics to satisfy these conditions. First, they must travel stably through the bloodstream without easily penetrating normal cells. Conversely, they must accumulate selectively in cancerous tissue and release the drug only after entering the cancer cells. Furthermore, it must be possible to track the drug’s path and confirm its accumulation sites after treatment. To meet these requirements, drug delivery systems that combine multiple functions into a single nanoparticle are being developed.
At the very core of these nanotechnology-based drugs are gold or iron nanoparticles measuring approximately 10 nm in size. While ingesting ordinary metals as-is can pose problems, gold or iron oxide nanoparticles—reduced to the nanoscale—are being utilized in medical research and diagnostic imaging when subjected to appropriate surface treatment. Furthermore, because these nanoparticles can be tracked using imaging equipment such as MRI, they can help monitor how the drug moves within the body. In other words, these nanoparticles serve as the core framework of the drug and enable the tracking of its movement.
A polymer structure called Cys-(p-Asp)-PEG is bound to the outer surface of the nanoparticles. First, “Cys” is an abbreviation for cysteine. Cysteine is an amino acid containing a sulfur atom, and sulfur atoms have the property of bonding very strongly with metals. Therefore, cysteine acts as a link between the metal nanoparticles and the external polymer structure. To use a human body analogy, it plays a role similar to that of a joint. Just as joints connect bones and maintain stability, cysteine also helps maintain the stability of the nanoparticle structure so that it does not easily deform or break.
The “p” in p-Asp, which is linked to cysteine, stands for “poly.” In other words, p-Asp refers to a structure composed of many aspartic acid (Aspartic acid) units linked together. Aspartic acid is an amino acid that is highly soluble in water and readily binds to ions. In this drug, it serves as the underlying framework that strongly binds to CAP—which will be explained later—and securely anchors it.
Finally, the PEG (polyethylene glycol) linked to p-Asp plays a role similar to that of sensory nerves in the human body. PEG is a water-soluble polymer that envelops the outermost layer of the drug, helping it move stably through bodily fluids. It also prevents the drug from being easily eliminated from the body and increases the likelihood of it reaching cancerous tissue. In this way, Cys-(p-Asp)-PEG forms the structure that envelops the exterior of the nanoparticle.
Now that it has a spine, joints, a supporting framework, and even sensory nerves, it’s time to create the flesh and skin. Since the most important function of this drug is cancer treatment, it naturally must contain the therapeutic agent. However, if the therapeutic agent is left exposed to the outside, it could affect normal tissue and cause serious side effects. To prevent this, the therapeutic agent is enclosed within a protective layer called CAP. CAP is composed of calcium phosphate (Ca₃(PO₄)₂) compounds and is relatively stable in a neutral environment, preventing the therapeutic agent from being easily exposed. However, in an acidic environment, it gradually decomposes, releasing the therapeutic agent inside. Both CAP and the therapeutic agent are linked to the p-Asp described earlier, and this structure completes the nanoparticle-based drug delivery system.
Let’s now examine the process by which the drug actually exerts its effect. Conventional anticancer drugs circulated through the body via the bloodstream, penetrating various cells without distinguishing between cancer cells and normal cells. As a result, not only cancer cells but also normal cells were damaged. In contrast, drugs utilizing nanotechnology are more likely to accumulate selectively in cancer tissue while circulating through the bloodstream, thanks to the functions of PEG and other components. Furthermore, even if the nanoparticles enter normal tissue, CAP does not easily degrade in a neutral environment, so the therapeutic agent is not released. However, in the relatively acidic microenvironment of cancer tissue or around cancer cells, CAP degrades, releasing the therapeutic agent, which then exerts its anticancer effect inside the cancer cells. Additionally, because the nanoparticles remain in the body, they can be used with imaging equipment such as MRI to monitor drug distribution and treatment progress.
As such, drug delivery technology using nanoparticles has the potential to reduce damage to normal tissue and enhance therapeutic efficacy compared to conventional anticancer treatments. However, not all nanoparticle-based anticancer drugs are already widely used in clinical practice; while some are being utilized in actual medical settings, various technologies are still undergoing ongoing clinical trials and research. It is expected that as these technologies continue to advance, they will significantly contribute to improving the efficacy of cancer treatment while reducing side effects.
