Super-selective molecular delivery system of metastatic lymph node using nanobubbles and ultrasound

本研究的目的是利用纳米气泡(NBS)和超声(US)建立一种超选择性的淋巴管转移的分子递送系统。我们使用的是MXH10/Mo-LPR/LPR小鼠，表现出显著的全身淋巴病变，有适当的腋窝淋巴结(PAN)和髂下淋巴结(SiLN)，直径为6-12 mm。首先，我们确定了位于头颈部、四肢、胸腹部的22个不同的淋巴结。转移途径是通过SiLN的传出淋巴管，转移的发生率取决于注射的细胞数量、注射时间和SiLN的体积。接下来，我们利用NBS和US的分子给药方法研究了药物对淋巴结转移的给药效率。研究发现，与在没有NBS的情况下使用US相比，在有NBS的情况下暴露于US可以增加荧光素向淋巴通道附近的淋巴细胞的输送。

The purpose of this study was to develop a super-selective molecular delivery system of lymph node metastasis via lymphatic vessels using nanobubbles (NBs) and ultrasound (US). We used MXH10/Mo-lpr/lpr mice exhibiting remarkable systemic lymphadenopathy, with proper axillary lymph nodes (PALNs) and subiliac lymph nodes (SiLNs) that are 6 to 12 mm in diameter. First, we identified 22 different LNs situated in the head and neck, limbs, thoracic and abdominal regions. The metastasis route was found to be via the efferent lymphatic vessels of the SiLN, and metastasis incidence depended on the number of cells injected, the injection duration and the SiLN volume. Next, we investigated drug delivery efficiency to the lymph node metastasis by the molecular delivery method using NBs and US. It was found that exposure to US in the presence of NBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared to the use of US in the absence of NBs.