黑色素瘤,新型纳米系统 z-bo 2020-10-28 370

　　In a recent study, Professor Ronit Satchi-Fainaro of the Department of Physiology and Pharmacology of TAU Sackler School of Medicine, Tel Aviv University, and others developed an innovative nanotechnology drug delivery system that significantly improved aggressive skin Cancer melanoma has a therapeutic effect. Nanocarriers are biocompatible and biodegradable polymers containing glutamic acid repeating units. It brings together two drugs from different families that have been proven effective for melanoma: BRAF inhibitors (dublafenib) and MEK inhibitors (selmethinib, approved for children with neurofibromatosis type I).

　　Professor Satchi-Fainaro said: “One of the main obstacles to biological therapy is that cancer cells become drug-resistant after a period of time. By precisely delivering two or more target drugs, they can be combined simultaneously from different directions. I believe we can do it. By vigorously attacking cancer cells, we can delay or prevent the development of this resistance. It is done in the form of a mixture of multiple drugs, but even when administered at the same time, due to basic parameters (such as tumor survival Time), they may also reach the tumor at the same time. No, the blood flow and the time it takes for each drug to reach the tumor tissue. Therefore, in most cases, the drugs cannot work at the same time, which prevents them from getting the best Synergistic activity. In response to these problems, the researchers developed an innovative, efficient and biodegradable drug delivery system. Two drugs known to be effective for melanoma, dabrafenib and sermitinib, were selected and co-delivered to Tumors. The drug nanocarrier selected for this task is called PGA, a kind of glutamate. The nanocarrier was developed in the laboratory of Professor Satchi-Fainaro several years ago and successfully tested animal models to treat pancreatic cancer and breast cancer And ovarian cancer. Researchers first determined the optimal ratio of these two drugs based on the level and type of toxicity and the resistance mechanism of cancer cells to each drug. Ultimately, it guarantees maximum efficacy, minimum toxicity and Optimal synergy. Another important advantage of co-administration is the low dose. Compared with each drug, the dose required when administered separately is much lower. The next step is to use chemical modification to make the polymer carrier and the Choose drug cross-linking. The combined system can be completely and safely distributed throughout the body without harming healthy tissues. After reaching the cancer cells, the nanocarrier will encounter the proteins in cathepsin, which are highly activated in malignant tumors. The protein breaks down the polymer, activates it, and releases the drug that binds to the tumor. The test results of the mouse melanoma model showed encouraging results. The nanocarrier can deliver two drugs to the tumor, and then release them simultaneously to the tumor. In vivo. The effective dose of the tumor site is about 20 times that of the drug delivered alone. In addition, the duration of the therapeutic effect achieved by the drug delivered by the nanocarrier is 2-3 times that of the control group and the group treated with free drug.

　　According to the researchers, the new platform can achieve a low dose, about one-third of the dose required for a traditional drug cocktail. Overall, the treatment is safer and more effective. If necessary, the dose allowed by the new method is much higher than the maximum dose allowed by the current method, which further improves the therapeutic effect.