Alexander Stoner Dr. Steven Lenhert BSC4424 4/23/20 Miniaturization of Drug Screening Methodology Cancer is a collection of diseases that cause one out of every six deaths, making it the second leading cause of death worldwide. All cancers share a common theme of uncontrollable cell growth and division, spreading across the body and transforming functional organs to nonfunctional tumors. Despite this horrible statistic, cancer survival rates have slowly increased since the 1960’s, as treatment options have progressed, and technology has advanced. Cancer can be treated with a variety of methods, with chemotherapy as the most popular treatment option for most types of the disease. The use of molecules to treat diseases began at the start of the 20th century, with German chemist Paul Ehrlich. Ehrlich coined the term “chemotherapy”, or the use of chemicals to treat disease, and was the first to document the effectiveness of animal testing in the efficiency of molecules for potential effectiveness against diseases. Following Ehrlich in 1935, the National Cancer Institute (NCI) was the first to set up an organized program in cancer drug screening. This program was the first to test a broad array of compounds, collaborating both interinstitutional and internationally as well. This program ultimately screened over 3,000 compounds using the murine S37 as the model system. Since then, the drug screening process has evolved into the various systems currently in use today: classical pharmacology and reverse pharmacology. Despite the incredible progress we’ve made in the field of treating diseases with drugs, the process of testing possible chemical treatments leaves some to be desired. The current method of screening for the effects of compounds on cells involves microtiter plate technology that uses microwells. While this method has the capability of screening hundreds of thousands of compounds at once, it requires quite a large amount of materials. In the US alone, $50 million to $2 billion dollars go into the cost of the required cells, reagents, and compounds alone. Furthermore, the current method of drug screening isn’t incredibly time efficient, as the cells used for testing require time to grow. Therefore, a possible solution is to miniaturize the drug screening process, allowing more compounds to be screened at once, whilst also reducing the cost of screening. A solution to this problem proposed by Kusi-Appiah and their research group is outlined in their recent publication Biomaterials. The technology to be utilized involves liposome microarrays, in which the compounds in question are placed onto a surface, and then cultured cells are placed on (or near) that surface. The cellular reaction between the compound and the cell is then analyzed and whether the compound demonstrates the desired activity is determined. This proposed solution is not without its limitations. Kusi-Appiah et al. detail how the main challenge in the microarray format is delivering a sufficient dosage of the compound to the cell without cross-contamination. However, this new type of microarray will be based on the usage of lipid multilayer structures. Because lipids are not soluble in water, their ability to encapsulate compounds in combination with their hydrophobicity will allow them to deliver the molecules to cells. Furthermore, dip-pen nanolithography (DPN) will be the method of creating these multilayer lipid structures. DPN is a lithography method used to pattern surfaces with specific molecules, which in turns allows for the precise control of the thickness of the lipid multilayer. By manipulating the lipid multilayer thickness, the exact dosage of the drug that the cell will receive can be fine-tuned and controlled if needed. Kusi-Appiah et al. demonstrated the process of utilizing lipid multilayer microarrays for drug delivery via fluorescently labeled lipids and cytotoxic lipophilic drugs. Corresponding toxicity was then assayed. Ultimately, KusiAppiah et al. determined that their lipid multilayer microarrays were suitable for the delivery of molecules to cultured cells, without significant cross-contamination of other cells. The lipid multilayer microarrays not only allow for more assays per unit area than the standard microtiter plates, the microarrays also require smaller dosages of the drug for efficient assays to occur. Finally, with the small number of cells needed to test compounds with, it is possible that this method could be used to screen drugs on “primary cells”. Primary cells are cells taken directly from living tissue, e.g a biopsy done in a cancer screening. While the results from this research are promising, the technology is still not widely utilized today. I believe this could be due to the amount of time it takes to replace our existing technology with modern nanotechnology. Implementing new technology around the world takes time no matter how innovative it is. Furthermore, this technology shows incredible promise in the world of personalized medicine. Cancer treatment and chemotherapy could be changed forever if personalized compounds were developed to treat each individual patient. Works Cited DeVita, Vincent T., and Edward Chu. "A history of cancer chemotherapy." Cancer research 68.21 (2008): 8643-8653. Kusi-Appiah, Aubrey E., et al. “Lipid Multilayer Microarrays for in Vitro Liposomal Drug Delivery and Screening.” Biomaterials, vol. 33, no. 16, 2012, pp. 4187–4194., doi:10.1016/j.biomaterials.2012.02.023. Lage, Olga, et al. “Current Screening Methodologies in Drug Discovery for Selected Human Diseases.” Marine Drugs, vol. 16, no. 8, 2018, p. 279., doi:10.3390/md16080279. Roser, Max, and Hannah Ritchie. “Cancer.” Our World in Data, 3 July 2015, ourworldindata.org/cancer.
