Department of Neurology and Stroke Center, The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou 510632, China.
Department of Neurology and Stroke Center, The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou 510632, China.
J Control Release. 2021 Mar 10;331:270-281. doi: 10.1016/j.jconrel.2020.09.051. Epub 2020 Oct 1.
High intensity focused ultrasound (HIFU) has been widely used in clinical treatment of cervical cancer for its non-invasiveness and sharp treatment margins with very low complication rates. However, how to intensify the therapeutic efficacy of HIFU by specifically focusing the ultrasound energy on targeting pathological tissues is still a bottleneck for it to realize successful cancer ablation. Herein, a multifunctional organic-inorganic hybrid nanovesicles, by coating ultrathin silica shell on the surface of poly (lactic-co-glycolic acid) (PLGA) loaded with perfluorocarbon (PFOB), hydrophobic antitumor ruthenium complex (RuPOP) and superparamagnetic FeO, has been designed to achieve synchronous ultrasound (US)/magnetic resonance imaging (MR) dual mode imaging-guided HIFU-triggered chemotherapy. The introduction of PFOB in this nanosystem could cause phase transition and make it gasification to cause collapse of the outer ultrathin silicon shell under HIFU irradiation, which results in enhanced intensive mechanical stress during blasting and enhanced therapeutic effect. The blasting behavior of this nanosystem triggered by HIFU also induced the on-demand RuPOP burst release in tumor site, thus maximizing the inhibition on residual tumor induced by inhomogeneous HIFU ablation. Taken together, this treatment strategy could overcome the inevitable tumor recurrence and significantly reduces systemic side effects of HIFU, thus could be further developed for noninvasive cancer therapy.
高强度聚焦超声（HIFU）由于其非侵入性和治疗边缘锐利，并发症发生率非常低，已广泛应用于宫颈癌的临床治疗。然而，如何通过将超声能量特异性聚焦在靶向病理组织上来增强 HIFU 的治疗效果，仍然是其实现成功癌症消融的一个瓶颈。在此，我们设计了一种多功能有机-无机杂化纳米囊泡，在负载全氟碳（PFOB）、疏水性抗癌钌配合物（RuPOP）和超顺磁 FeO 的聚乳酸-羟基乙酸共聚物（PLGA）表面涂覆超薄二氧化硅壳，以实现同步超声（US）/磁共振成像（MR）双模成像引导的 HIFU 触发化疗。该纳米系统中 PFOB 的引入会引起相变，并在 HIFU 照射下使其气化，导致外超薄硅壳坍塌，从而在爆破时产生更强的密集机械应力，增强治疗效果。HIFU 触发的纳米系统的爆破行为还会导致肿瘤部位按需释放 RuPOP，从而最大限度地抑制不均匀 HIFU 消融引起的残留肿瘤。总之，这种治疗策略可以克服不可避免的肿瘤复发，并显著降低 HIFU 的全身副作用，因此可以进一步开发用于非侵入性癌症治疗。
