Big things come in small packages, and Dr. Hongsik Cho is very familiar with this phenomenon. When wefirst introduced Dr. Cho in August 2016, he was beginning work on his 2-year Arthritis Foundation-funded project, “A Novel Method of Detecting and Treating Early PTOA Using Smart Nanosome”. He and his team are studying two things: a new drug and a new drug delivery system. The drug, called TPCA-1, works to prevent inflammation caused by post-traumatic osteoarthritis (PTOA). The drug delivery system uses small packets called nanosomes that contain TPCA-1 and a fluorescent dye that illuminates the nanosomes’ path once injected into mice.
本研究的第一个目标是找到一种早期诊断PTOA的方法。赵教授解释说，治疗PTOA的问题之一是，在早期发现受损的软骨组织。病变可能太小而无法发现。但是Cho博士和他的团队已经找到了一种方法，在开始阶段使用纳米体来诊断PTOA。
Dr. Cho says that healthy cartilage contains smooth collagen without any shown areas of bonded DNA. When collagen is damaged, these areas are unhidden and the surface of cartilage erodes. The team has developed a binding agent that is attracted to damaged collagen in cartilage. The binding agent combines with the fluorescent dye in the nanosome, and together they find the damaged collagen and can identify even the smallest lesions. The nanosomes target the injury with the binding agent and mark the injury with fluorescent dye.
“At the time when the first lesion forms after an injury,” Dr. Cho explained, “the lesion may not be detectable by normal means. But the pathways that cause cartilage degeneration are already beginning.”
Cho博士和他的团队发现，关节上的机械应力，就像PTOA一样，会导致导致软骨变性的化学多米诺效应(或途径)。当胶原蛋白受到影响，软骨受损时，这些通路就会发生。TPCA-1药物被设计用来阻断软骨损伤引起的炎症通路。然而，当高剂量和/或长时间使用TPCA-1时，会产生有害的副作用。通过使用携带TPCA-1的靶向纳米体系统，该团队可以控制药物浓度以及药物被递送的次数和频率。
The study’s second and third goals are finding a way to make measurements in individual joints to track disease progression and determining how effective the drug treatment is. The project is in this stage. The team has detected OA in the mice they are treating with the targeted delivery system of TPCA-1. During the next 6 months, they will monitor the mice, measure lesions andOA progressionwhile looking for the optimal dose of TPCA-1. While Dr. Cho is optimistic about the results so far, he says (providing they are still getting successful results) it may be at least 5 years until human trials are possible. “There are still a lot of questions to answer,” he said. “We are still looking at things like what will be the most effective route of delivery of the drug. Do we give it intravenous, inject it directly into the joint, or inject it intramuscularly? This may work differently for humans.”
In the meantime, Dr. Cho and his team will use what they have learned about nanosomes as a platform for new applications of their drug delivery method. They will continue to study other molecules that may be involved in different disease pathways in search of a cure.
Dr. Cho is an assistant professor of orthopedic surgery at The University of Tennessee Health Science Center in Memphis, TN.
Related Resources:
- Researchers on the Path to a Cure – Spotlight on Dr. Christine Beeton
- Researchers on the Path to a Cure – Spotlight on Dr. C. Michael Stein
- Researchers on the Path to a Cure – Spotlight on Salah Ahmed
- Researchers on the Path to a Cure – Spotlight on Dr. Rae Yeung