Faculty Editor: Professor Jeffrey DaCosta
Nanomedicine, or the medical application of nanotechnology, is an emerging field with great potential for improving public health. Currently, new forms of nanotechnology are being created and explored for more effective prevention, diagnosis, and treatment of cancers. This research utilizes the natural, microscopic scale of biological phenomena to develop precise solutions that can directly target tumors. Nanoscale devices are between 100 to 10,000 times smaller than human cells, which allow them to easily interact with biomolecules both on the surface and inside cells. At such a small size, nanodevices can be tailored to exhibit specific properties critical to disease targeting (Nanomedicine European Technology Platform, 2019). In recent years, scientists have been working to develop new nanotechnologies to ameliorate cancer treatment across all stages. These devices, called “nanorobots,” are highly sought after to destroy and dispel tumor cells while leaving healthy tissue untouched.
Angiogenesis is the growth of blood vessels from the existing vasculature, and it is a key factor in the survival and proliferation of cancer cells. Increased accessibility to blood vessels allows tumor cells to have sufficient supplies of oxygen and nutrients, as well as the proper removal of waste products, and tumor cells express angiogenic factors that serve as activators of new blood vessel formation (National Cancer Institute, 2018). Thus, angiogenesis is an attractive target for cancer therapeutics as it is a hallmark of cancer metastasis and is found in many different types of cancer. In conjunction with conventional cytoreductive cancer treatments, antiangiogenic agents present themselves as comprehensive, strategical solutions to elevating the long-term survival rates of cancer patients.
Researchers at the National Center for Nanoscience and Technology in China sought to create a drug that targets angiogenesis through the use of DNA origami as a nanorobot system. DNA origami is a recently developed technique that uses DNA as a building block for the synthesis of nanoparticles. The design is comprised of a several-hundred base-pair piece of single-stranded DNA as the scaffold, with several small pieces of single-stranded DNA as staples used to contort the scaffold into the desired shape (Li et al., 2018). It exploits the intrinsic chemical properties of DNA to create complex nanostructures via self-assembly.
The researchers used this technique to create a nanoparticle to deliver thrombin enzymes, which are crucial for blood clotting, to cancer cells to function as antiangiogenic agents. DNA nanorobots were developed from a flat, rectangular DNA origami sheet, 90 nanometers by 60 nanometers in size, and loaded with four thrombin molecules. Also attached on the surface of the nanorobot is a DNA aptamer, which is similar to an antibody given its specificity and affinity towards its target. In this model, the aptamer targets a protein called nucleolin, which is highly prevalent on the surface of tumor endothelial cells. Upon binding to a tumor blood vessel surface, the nanorobot is activated and releases thrombin, prohibiting blood flow to the angiogenic vessel (Li et al., 2018).
The scientists explored this mechanism through mouse model studies, in which they tested this method in breast, melanoma, ovarian, and lung cancer cells (Li et al., 2018). Their results were promising, for the median survival time increased from 20.5 days to 45 days with the nanorobot treatment compared to saline alone in the melanoma model. Breast cancer and melanoma are known to have significant vascularization, while ovarian and lung cancers are known to be less vascularized. Despite these differences, the nanorobots were able to exert antitumor activity in all four models as shown by survivor curves and tumor weights measured in each setting, demonstrating how they are clearly able to inhibit tumor progression.
Their proposed system is innovative, especially considering how naked thrombin is unable to survive for long periods of time in circulation and is unable to discriminate between healthy tissue and cancerous cells, necessitating a nanorobot for higher levels of control. Nanotechnology now allows scientists to work at previously unimaginable scales, which is a significant advantage for oncology treatment as the therapy has the potential to manipulate a variety of molecular targets with more precision. As all solid tumor-feeding vessels are essentially the same, depriving tumors of nutrients and oxygen poses an attractive strategy for combating cancer.
- Angiogenesis Inhibitors. (2018, April 2). Retrieved October 17, 2019, from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet.
- Li, S., Jiang, Q., Liu, S., Zhang, Y., Tian, Y., Song, C., … Zhao, Y. (2018). A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nature Biotechnology, 36(3), 258–264. doi: 10.1038/nbt.4071
- What is Nanomedicine? (2019). Retrieved October 17, 2019, from https://etp-nanomedicine.eu/about-nanomedicine/what-is-nanomedicine/.