动物造模,复发性脑癌 z-bio 2021-02-19 344

　　A new study from the University of Michigan shows that a new synthetic protein nanoparticle can slide across the almost impermeable blood-brain barrier in mice, and can deliver cancer-killing drugs directly to malignant brain tumors.

　　 This study is the first to prove that intravenous drugs can cross the blood-brain barrier.

　　 This discovery may one day provide new clinical therapies for the treatment of glioblastoma, which is the most common and aggressive brain cancer in adults, and its incidence is increasing in many countries. Today, the median survival time of patients with glioblastoma is about 18 months. The average 5-year survival rate is less than 5%.

　　 Combined with radiation, the intravenous injection therapy of the UM team can result in long-term survival of seven out of eight mice. When the glioblastoma of those seven mice recurred, their immune response began to work to prevent the re-growth of the cancer without any other therapeutic drugs or other clinical treatments. Joerg Lahann, a professor at the School of Chemical Engineering of Wolfgang Poly University and co-senior author of the study, said: “For us, this is still a miracle.” “In places where we expect to see some degree of tumor growth, They did not form when we challenged mice. I have been working in this field for more than 10 years and have not seen anything like this."

　　The research results show that the combination of therapeutic drugs and nanoparticle delivery methods by the UM team not only eradicates the primary tumor, but also generates immune memory, or has the ability to recognize and attack the remaining malignant cancer cells faster. Maria Castro, a professor at the School of Neurosurgery at RC Schneider University and co-senior author of the study, said: "This is an important step towards clinical implementation." "This is the first proof that it can be systemic or intravenous. The study of the ability of internal delivery of therapeutic drugs, which can also cross the blood-brain barrier to reach tumors."

　　 Five years ago, Castro knew how she wanted to target glioblastoma. She wants to stop the signal sent by a cancer cell, namely STAT3, in order to trick immune cells into a safe passage in the brain. If she can shut down the pathway with inhibitors, the cancer cells will be exposed and the immune system can eliminate them. But she has no way to overcome the blood-brain barrier.

　　 She attended a seminar of the Institute of Biological Interface led by Lahann, and the two discussed this issue. Lahann's group began to study nanoparticles that can transport STAT3 inhibitors across the blood-brain barrier.

　　 A protein called human serum albumin in the blood is one of the few molecules that can cross the blood-brain barrier, so Lahann's research team used it as a structural building block for nanoparticles. They used synthetic molecules to link these proteins, and then linked STAT3 inhibitors to a peptide called iRGD, which can be used as a tumor homing device.