Celastrol（CST）在多种癌症中具有积极的药理效应，但由于其溶解度差和全身毒性的限制，临床应用受到限制。铁氧体（Fe3O4）具有大的比表面积，可通过无机修饰来功能化，形成复杂的磁性药物传递系统。本文利用柠檬酸和聚乙二醇（PEG）通过Mitsunobu反应对Fe3O4进行表面修饰，然后与CST共价结合。最后，利用聚乳酸-共聚乙二醇酸（PLGA）构建了含有全氟丙烷（C3F8）和Fe3O4-PEG2K-CST颗粒的磁性微泡（MMBs）作为负载。体外研究表明，超声波介导的MMBs与无超声介导的MMBs、空白MMBs或游离CST相比，对VX2细胞的增殖具有更好的抑制作用。在超声模式下，MMBs具有良好的成像特性。在高机械指数的作用下，MMBs经过空化效应崩溃，释放内部的Fe3O4-PEG2K-CST。在酸性环境下，CST随后被输送到肿瘤微环境中。在磁共振成像T2模式下，在治疗前后，肿瘤区域观察到特定的低信号，而周围器官的信号强度没有明显变化。治疗后，对带瘤兔组织的病理检查显示，铁元素在肿瘤区域的几个凋亡细胞中积累，其他区域没有明显异常。因此，超声波介导的MMBs可以显著提高实体肿瘤对药物的摄取，并具有良好的生物安全性。© 2023. Controlled Release Society.

Celastrol (CST) has positive pharmacological effects on various cancers, but clinical application is limited because of poor water solubility and systemic toxicity. Ferric oxide (Fe3O4) has a large specific surface area and can be functionalized by inorganic modification to form complex magnetic drug delivery systems. Herein, Fe3O4 was surface-modified with citric acid and polyethylene glycol (PEG) (via) the Mitsunobu reaction and then covalently bound to CST. Finally, magnetic microbubbles (MMBs) containing perfluoropropane (C3F8) and Fe3O4-PEG2K-CST particles were constructed with poly(lactic-co-glycolic acid) (PLGA) as the shell membrane. In vitro studies showed that ultrasound-mediated MMBs exhibited improved inhibition of VX2 cell proliferation compared to inhibition achieved using MMBs without ultrasound mediation, blank MMBs, or free CST. In ultrasound mode, MMBs have favorable imaging properties. After the application of a high mechanical index, MMBs collapse through the cavitation effect, releasing their internal Fe3O4-PEG2K-CST. The CST is then delivered to the tumor microenvironment under acidic conditions. In magnetic resonance imaging T2 mode, a specific hypointense signal was observed in the tumor area compared with that before treatment, whereas no significant change occurred in the signal intensity of the surrounding organs. After treatment, pathological examination of tumor-bearing rabbit tissues showed that iron elements accumulated in several apoptosis cells in the tumor area, with no apparent abnormalities found in other areas. Thus, ultrasound-mediated MMBs could significantly improve the drug uptake of solid tumors and inhibit tumor growth with favorable biological safety.© 2023. Controlled Release Society.