2025-02-11 作者：ZJ 来源：文献：Dual ultrasound-activatable nanodroplets for highly-penetrative and efficient ovarian cancer theranostics
文献链接：https://pubs.rsc.org/en/content/articlelanding/2020/tb/c9tb02198a
作者：Chao Yang,Yi Zhang,Yuanli Luo,Bin Qiao,Xingyue Wang,Liang Zhang,Qiaoqi Chen,Yang Cao,Zhigang Wang and Haitao Ran
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原文摘要：The selective delivery and deep intertumoral penetration of nanosensitizers remain challenging in the fabrication of sonodynamic therapy (SDT) platforms. In this work, we rationally constructed dual ultrasound (US)-activatable nanodroplets (NDs)/nanoliposomes/nanosensitizers with perfluoropentane (PFP) in the core, hematoporphyrin monomethyl ether (HMME) in the phospholipid shell and folate (FA)-conjugated to the surface (collectively termed FA-H@NDs). We aimed to validate the feasibility of these FA-H@NDs for FA receptor (FR)-overexpressed ovarian cancer theranostics. The ND formulations were based on PFP that can undergo acoustic droplet vaporization (ADV) when exposed to US irradiation. The ADV phenomenon disrupts the adjacent vasculature, and the resistance to drug diffusion within the tumor can be decreased, enabling nanosensitizers to more deeply penetrate into the inner tissue far from the intertumoral vasculature. These FA-H@NDs assisted by US irradiation can also induce the production of excess reactive oxygen species (ROS) and consequently trigger tumor cell/tissue apoptosis and necrosis. Furthermore, this therapeutic process can be guided and monitored by US/photoacoustic (PA) dual-modal imaging. This work established a new paradigm for highly efficient ovarian cancer theranostics based on the rational utilization of dual US-activatable NDs.
FA-PEG2000-DSPE是一种化合物。它由叶酸（FA）、聚乙二醇（PEG2000）和二硬脂酰磷脂酰乙醇胺（DSPE）组成。其中，PEG2000 赋予了该化合物良好的水溶性和生物相容性。DSPE 是一种磷脂，具有两亲性，能够在水中自组装形成脂质体等结构。而叶酸则为其提供了靶向功能。由于许多tumor细胞表面过度表达叶酸受体，该化合物可以通过叶酸与tumor细胞表面的受体特异性结合，实现对tumor细胞的靶向输送。可以用于制备载药脂质体等药物输送系统，提高药物对tumor细胞的选择性和Therapeutic effect ，同时降低对正常组织的副作用。基于此构建了双超声（US）激活的纳米液滴（NDs）/纳米脂质体/纳米增敏剂，核心为全氟戊烷（PFP），磷脂壳中的血卟啉单甲基醚（HMME）和叶酸（FA）结合到表面（统称为FA-H@NDs)。
图：FA-H@NDs的合成过程示意图。
FA-H@NDs的制备
FA-PEG2000-DSPE，DSPC，胆固醇和HMME溶解在三氯甲烷中。然后，将溶液旋转蒸发形成薄膜。接下来，剥薄膜，在超声器的辅助下溶解在磷酸盐缓冲盐水（PBS）中。随后，在上述溶液中加入PFP。然后，将溶液在冰浴中进行超声处理，然后，在低温离心后收集FA-H@NDs。在H@NDs的制造过程中，不同于用PEG2000-DSPE取代FA-PEG2000-DSPE。
图：双us激活的FA-H@NDs的Treatment 功能示意图
结论：FA-H@NDs通过被动EPR效应和与FA受体阳性SKOV3tumor细胞的选择性结合，容易从体内循环的卵巢tumor区域积累，可以通过PA成像监测。在US照射下，这些FA-H@NDs发生ADV并转化为气泡，进一步增强了US成像和NDs的穿透能力。此外，这些FA-H@NDs在US照射的辅助下产生了过量的ROS，从而触发了卵巢cancer细胞/组织的清除。评估结果显示，体外SDT效率高，体内SDT有tumor抑制作用。
