Molecular Self-Assembling Antioxidants (RNP) for Cancer Therapy

The drug delivery system (DDS), which reduces side effects and improves the impact by encapsulating existing drugs in carriers and transporting them to the target site, is a method of suppressing the rise in drug prices and improving the patients’ quality of life (QOL). These systems, which mainly carry anti-cancer drugs to solid tumors, have been proven effective, and some have already been approved. However, recent clinical studies have revealed that the accumulation of nanoparticles in tumors is only a few percent. Besides, the drugs encapsulated in the carrier leak out during circulation in the body, which decreases their efficiencies. To solve these problems, we have recently proposed the concept of “molecular self-assembling drugs”, which means that the biological functions and therapeutic effects that cannot be obtained with low molecular weight compound alone can be controlled by organizing small molecular weight drugs. Here, the author introduces one of the examples of the molecular self-assembling drugs as reactive oxygen species scavengers (antioxidants). Overproduced ROS change the balance of the redox system in vivo, leading to severe body dysfunction, which is so-called oxidative stress. Although numerous antioxidants have been developed, including natural compounds such as vitamins C, E, and astaxanthin to remove the overproduced ROS, most failed clinically and have been merely used as supplements. A low molecular weight antioxidant has several drawbacks, such as rapid excretion from the body and dysfunction of mitochondria in normal cells, leading to a very low to no therapeutic window. We installed the antioxidants into the amphiphilic block copolymers via the covalent bond. They spontaneously form polymeric micelle in aqueous media with several tens of nanometer sizes (abbreviated as redox nanoparticle; RNP). RNP reduced internalization in normal cells due to their sizes and prevented mitochondrial dysfunction, which expanded the therapeutic window. Because the adverse effect of RNP is relatively low, we can apply them to versatile oxidative stress-related diseases such as ulcerative colitis, Alzheimer’s disease, liver fibrosis, and so on. Tumor-microenvironment is known to be severely inflamed with a high level of ROS, which further exacerbates it and attenuates its therapeutic efficacy. Therefore, we have applied RNP to investigate the effect on tumorigenesis, progression, and metastasis. The results in in vitro and in vivo are summarized in this chapter.