Optical Modulation of the Blood-Brain Barrier for Glioblastoma Treatment

作者：Qi Cai, Hanwen Fan, Xiaoqing Li, Monica Giannotta, Robert Bachoo, Zhenpeng Qin · 发表于：BIO-PROTOCOL · 年份：2024 · DOI：10.21769/bioprotoc.4920 · 被引用次数：6 · 研究领域：Photoacoustic and Ultrasonic Imaging、Ultrasound and Hyperthermia Applications、Nanoplatforms for cancer theranostics

The blood-brain barrier (BBB) is a major obstacle to the diagnostics and treatment of many central nervous system (CNS) diseases. A prime example of this challenge is seen in glioblastoma (GBM), the most aggressive and malignant primary brain tumor. The BBB in brain tumors, or the blood-brain-tumor barrier (BBTB), prevents the efficient delivery of most therapeutics to brain tumors. Current strategies to overcome the BBB for therapeutic delivery, such as using hyperosmotic agents (mannitol), have impeded progress in clinical translation limited by the lack of spatial resolution, high incidences of complications, and potential for toxicity. Focused ultrasound combined with intravenously administered microbubbles enables the transient disruption of the BBB and has progressed to early-phase clinical trials. However, the poor survival with currently approved treatments for GBM highlights the compelling need to develop and validate treatment strategies as well as the screening for more potent anticancer drugs. In this protocol, we introduce an optical method to open the BBTB (OptoBBTB) for therapeutic delivery via ultrashort pulse laser stimulation of vascular targeting plasmonic gold nanoparticles (AuNPs). Specifically, the protocol includes the synthesis and characterization of vascular-targeting AuNPs and a detailed procedure of optoBBTB. We also report the downstream characterization of the drug delivery and tumor treatment efficacy after BBB modulation. Compared with other ba...