AsianScientist (Mar. 19, 2018) – A team of researchers at Institute for Basic Science (IBS) in South Korea have developed nanocontainers to deliver anticancer drugs at precise timings, to specific locations in the body. They published their findings in Angewandte Chemie International Edition.
Conventional anticancer chemotherapy often involves the use of drugs that are toxic not only to cancer cells, but to normal, healthy cells as well. This results in side effects that can compromise quality of life. Hence, methods for targeted delivery of chemotherapy drugs are needed.
In this study, a research group led by Dr. Park Kyeng Min at IBS has developed a carrier molecule that allowed targeted and controlled drug release. Thanks to a serendipitous observation, the researchers found that pumpkin-shaped molecules with short tails—mono-allyloxylated cucurbit[7]uril (AO1CB[7])—act as surfactants in water.
Most surfactants, like soap molecules in bubbles and phospholipids in cellular membranes, have small water-loving (hydrophilic) heads and long fat-loving (hydrophobic) tails that determine how they arrange in space. In contrast, AO1CB[7] is rather unconventional as it forms vesicles in water despite its short hydrophobic tail. Detailed analysis showed that the tails unite AO1CB[7] molecules into colloidal particles.
“Seeing AO1CB[7] form a cloudy solution when shaken in water was a surprise,” said Park. “We decided to take advantage of this property and use these vesicles as vehicles to carry anticancer drugs. Then, by controlling when and where the vesicles are broken, the drugs could be released on demand.”
Beyond helping AO1CB[7] to self-assemble, the hydrophobic tail is also light-responsive: it can react with molecules normally present in cells, such as glutathione, when irradiated by ultraviolet (UV) light. Similarly to a soap bubble popping, the reaction between the tails and glutathione molecules breaks the AO1CB[7] vesicles apart.
Rather than using a UV single-photon laser to promote the glutathione-hydrophobic tail reaction, the researchers employed a near infrared two-photon laser, which has the ability to penetrate deeper into tissues with increased accuracy. As the irradiated area is smaller, the drug delivery is confined to the targeted area, resulting in less damage to healthy tissue surrounding the tumor.
The research team applied this technology to deliver the chemotherapeutic drug Doxorubicin to cervical cancer cells (HeLa cells) in the laboratory. They observed that the drug was able to exit the vesicles, reach the nucleus of the cancer cells, and eventually kill them.
“These cell-level studies represent a proof-of-concept of the utility of AO1CB[7]. Now we want to extend this technology to animal models, such as cancer-bearing mice, to verify its practical use in different types of tumors,” said Park.
The article can be found at: Park et al. (2018) Mono-allyloxylated Cucurbit[7]uril Acts as an Unconventional Amphiphile To Form Light-Responsive Vesicles.
———
Source: Institute of Basic Science; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
