Purpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement.
Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated.
Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00± 0.1717 nm and an APS-loading efficiency of 54.89± 2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo.
Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.

Keywords: immune, immunoadjuvant, thermal ablation, PLGA, Chinese traditional medicine


中文翻译：

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黄芪多糖和金纳米棒的多功能纳米颗粒结合聚焦超声治疗乳腺癌。

目的：聚焦超声 (FUS) 是一种非侵入性方法，可产生热和机械破坏以及对癌症的免疫刺激作用。然而，单独的 FUS 消融似乎不足以产生一致的抗肿瘤​​免疫。在这项研究中，一种多功能纳米颗粒被设计用于增强 FUS 诱导的免疫效应并实现全身、持久的抗肿瘤免疫，以及成像和热增强。
材料和方法：通过简单的双乳液法构建包裹黄芪多糖 (APS) 和金纳米棒 (AuNR) 的 PEG 化 PLGA 纳米粒子，对其进行表征并测试其细胞毒性。在体外和体内分析了 PA 成像能力和热协同消融效率。还评估了体外对树突状细胞 (DC) 分化的免疫协同作用和体内免疫反应。
结果：获得的APS/AuNR/PLGA-PEG纳米粒子的平均直径为255.00±0.1717 nm，APS负载效率为54.89±2.07%，证明了它们的PA成像能力和体外和体内的高生物相容性。此外，所制备的纳米颗粒在体外细胞悬浮试验中获得了更高的坏死细胞率和诱导细胞凋亡率，在体内兔肝脏试验中获得了更大的坏死面积和降低的能量效率因子（EEF），并且具有显着的热协同作用。表现。特别是，纳米颗粒在体外上调了共培养的 DCs 上 MHC-II、CD80 和 CD86 的表达，随后吞噬功能下降并增强了白细胞介素 (IL)-12 和干扰素 (INF)-γ 的产生。此外，它们促进了肿瘤坏死因子 (TNF)-α、IFN-γ、IL-4、IL-10 和 IgG1 的产生（P< 0.001) 但不是 IgG2a。体内 FUS 后第 3 天免疫促进达到顶峰。
结论：多功能 APS/AuNR/PLGA-PEG 纳米粒子可作为 FUS 治疗的良好协同剂，促进实时成像，促进热消融效应，增强 FUS 诱导的免疫效应，具有潜在的应用前景。进一步的临床 FUS 治疗。

关键词：免疫 免疫佐剂 热消融 PLGA 中药