School of Aeronautic Science and Engineering, Beihang University, Beijing, 100191, P. R. China.
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
J Mater Chem B. 2021 Mar 17;9(10):2384-2393. doi: 10.1039/d0tb02788j.
Focused ultrasound (FU) is in demand for clinical cancer therapy, but the possible thermal injury to the normal peripheral tissues limits the usage of the ablative FU for tumors with a large size; therefore research efforts have been made to minimize the possible side effects induced by the FU treatment. Non-ablative focused ultrasound assisted chemotherapy could open a new avenue for the development of cancer therapy technology. Here, low intensity focused ultrasound (LIFU) for controlled quick intracellular release of small molecules (Mw ≤ 1000 Da) without acute cell damage is demonstrated. The release is achieved by a composite poly(allylamine hydrochloride) (PAH)/poly-(sodium 4-styrenesulfonate) (PSS)/SiO2 microcapsules which are highly sensitive to LIFU and can be effectively broken by weak cavitation effects. Most PAH/PSS/SiO2 capsules in B50 rat neuronal cells can be ruptured and release rhodamine B (Rh-B) into the cytosol within only 30 s of 0.75 W cm-2 LIFU treatment, as demonstrated by the CLSM results. While the same LIFU treatment shows no obvious damage to cells, as proved by the live/dead experiment, showing that 90% of cells remain alive.
聚焦超声（FU）在癌症临床治疗中有很大需求，但由于其对正常外周组织可能造成的热损伤，限制了消融 FU 在大肿瘤治疗中的应用；因此，研究人员致力于将 FU 治疗可能产生的副作用降到最低。非消融聚焦超声辅助化疗为癌症治疗技术的发展开辟了新途径。本研究通过低强度聚焦超声（LIFU）实现了对小分子（分子量 ≤ 1000 Da）的快速、可控的细胞内释放，而不会造成急性细胞损伤。该释放是通过对聚（盐酸烯丙胺）（PAH）/聚-（4-苯乙烯磺酸钠）（PSS）/SiO2 复合微胶囊的操控实现的，这种微胶囊对 LIFU 高度敏感，且能被微弱的空化效应有效破坏。共聚焦激光扫描显微镜（CLSM）的结果显示，在 0.75 W cm-2 的 LIFU 处理 30 s 内，B50 大鼠神经元细胞中的大多数 PAH/PSS/SiO2 胶囊即可破裂，将罗丹明 B（Rh-B）释放到细胞质中。而相同的 LIFU 处理对细胞没有明显的损伤，这一点通过死活细胞实验得到证实，90%的细胞仍然存活。
