State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Ultrasonography Department, The Fourth People's Hospital of Chongqing, Central Hospital of Chongqing University, Chongqing 400014, People's Republic of China.
Int J Nanomedicine. 2020 Jun 12;15:4151-4169. doi: 10.2147/IJN.S246447. eCollection 2020.
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.
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.
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.
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.
聚焦超声（FUS）是一种非侵入性方法，可产生热和机械破坏，并具有针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，设计了一种多功能纳米粒子，以增强 FUS 诱导的免疫效应，实现全身，持久的抗肿瘤免疫，以及成像和热增强。
通过简单的双乳液法构建了聚乙二醇化 PLGA 纳米粒子，其中包封了黄芪多糖（APS）和金纳米棒（AuNRs），并对其进行了表征和细胞毒性测试。分析了体外和体内的 PA 成像和热协同消融效率。还评估了体外对树突状细胞（DC）分化的免疫协同作用以及体内的免疫反应。
获得的 APS/AuNR/PLGA-PEG 纳米粒子的平均直径为 255.00±0.1717nm，APS 负载效率为 54.89±2.07％，证明了它们具有 PA 成像能力和体外和体内的高生物相容性。此外，在体外细胞悬浮液测定中，所制备的纳米粒子实现了更高的坏死细胞率和诱导的凋亡率，在体内兔肝测定中实现了更大的坏死面积和降低的能量效率因子（EEF），并具有显著的热协同性能。特别是，纳米粒子在体外共培养的 DC 上上调了 MHC-II、CD80 和 CD86 的表达，随后降低了吞噬功能并增强了白细胞介素（IL）-12 和干扰素（IFN）-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），但不促进 IgG2a 的产生。免疫促进作用在体内 FUS 后第 3 天达到峰值。
多功能 APS/AuNR/PLGA-PEG 纳米粒子可用作 FUS 治疗的出色协同剂，有利于实时成像，促进热消融效果，并增强 FUS 诱导的免疫效应，有望用于进一步的临床 FUS 治疗。
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