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.

中文翻译：

---

双重超声波可激活的纳米液滴，用于高度渗透性和高效的卵巢癌治疗。

在声动力疗法（SDT）平台的制造中，纳米敏化剂的选择性递送和深入的肿瘤间渗透仍然具有挑战性。在这项工作中，我们合理地构建了双超声波（US）激活的纳米液滴（NDs）/纳米脂质体/纳米敏化剂，其核心为全氟戊烷（PFP），磷脂壳中的血卟啉单甲醚（HMME）和叶酸（FA）偶联至表面（统称为FA-H @ NDs）。我们旨在验证这些FA-H @ NDs对于FA受体（FR）过表达的卵巢癌治疗的可行性。ND配方基于PFP，当暴露于US辐射时会发生声滴汽化（ADV）。ADV现象会破坏邻近的脉管系统，并且可以降低对肿瘤内药物扩散的抵抗力，使纳米增敏剂更深入地渗透到远离肿瘤间脉管系统的内部组织。这些由US辐射辅助的FA-H @ NDs还可以诱导产生过量的活性氧（ROS），从而触发肿瘤细胞/组织的凋亡和坏死。此外，该治疗过程可以通过US /光声（PA）双模态成像进行指导和监视。这项工作建立在合理利用双重美国可激活NDs的基础上，建立了高效卵巢癌治疗学的新范例。此治疗过程可以通过US /光声（PA）双模态成像进行指导和监视。这项工作建立在合理利用双重美国可激活NDs的基础上，建立了高效卵巢癌治疗学的新范例。此治疗过程可以通过US /光声（PA）双模态成像进行指导和监视。这项工作建立在合理利用双重美国可激活NDs的基础上，建立了高效卵巢癌治疗学的新范例。