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Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model
Nano-Micro Letters ( IF 31.6 ) Pub Date : 2021-06-19 , DOI: 10.1007/s40820-021-00666-8
Hai-Yi Feng 1, 2 , Yihang Yuan 1 , Yunpeng Zhang 2 , Hai-Jun Liu 1 , Xiao Dong 1 , Si-Cong Yang 1 , Xue-Liang Liu 1 , Xing Lai 1 , Mao-Hua Zhu 1 , Jue Wang 2 , Qin Lu 1 , Quanjun Lin 2 , Hong-Zhuan Chen 3 , Jonathan F Lovell 4 , Peng Sun 2 , Chao Fang 1
Affiliation  

  • Small-sized trastuzumab-targeted micelles (T-MP) were engineered using a surfactant-stripping approach that yielded concentrated phthalocyanines with strong near infrared absorption.

  • T-MP accumulated more in the lymph node (LN) metastases of orthotopic colorectal cancer compared to the micelles conjugated with control IgG.

  • Following surgical resection of the primary tumor, minimally invasive photothermal treatment of the metastatic LN with T-MP, but not the control micelles, extended mouse survival.

AbstractSection Abstract

Tumor lymph node (LN) metastasis seriously affects the treatment prognosis. Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration. Here, we speculate through introducing targeting capacity, the nanoparticle accumulation in LN metastases would be further enhanced for improved local treatment such as photothermal therapy. Trastuzumab-targeted micelles (< 50 nm) were formulated using a unique surfactant-stripping approach that yielded concentrated phthalocyanines with strong near-infrared absorption. Targeted micellar phthalocyanine (T-MP) was an effective photothermal transducer and ablated HT-29 cells in vitro. A HER2-expressing colorectal cancer cell line (HT-29) was used to establish an orthotopic mouse model that developed metastatic disease in mesenteric sentinel LN. T-MP accumulated more in the LN metastases compared to the micelles conjugated with control IgG. Following surgical resection of the primary tumor, minimally invasive photothermal treatment of the metastatic LN with T-MP, but not the control micelles, extended mouse survival. Our findings demonstrate for the first time that targeted small-sized nanoparticles have potential to enable superior paradigms for dealing with LN metastases.



中文翻译:

在原位结直肠肿瘤模型中用于淋巴结转移归巢和光热治疗的靶向胶束酞菁

  • 小型曲妥珠单抗靶向胶束 (T-MP) 采用表面活性剂剥离方法进行设计,可产生具有强近红外吸收的浓缩酞菁。

  • 与与对照 IgG 缀合的胶束相比,T-MP 在原位结直肠癌的淋巴结 (LN) 转移灶中积累更多。

  • 在手术切除原发性肿瘤后,用 T-MP 对转移性 LN 进行微创光热治疗,而不是对照胶束,延长了小鼠的存活时间。

摘要节摘要

肿瘤淋巴结(LN)转移严重影响治疗预后。研究表明,尺寸小于 50 nm 的纳米颗粒在静脉给药后可直接渗入 LN 转移灶。在这里,我们推测通过引入靶向能力,LN转移灶中的纳米颗粒积累将进一步增强,以改善局部治疗,例如光热疗法。使用独特的表面活性剂剥离方法配制曲妥珠单抗靶向胶束(<50 nm),该方法可产生具有强近红外吸收的浓缩酞菁。靶向胶束酞菁 (T-MP) 是一种有效的光热传感器,可在体外消融 HT-29 细胞。使用表达 HER2 的结肠直肠癌细胞系 (HT-29) 建立原位小鼠模型,该模型在肠系膜前哨 LN 中发生转移性疾病。与与对照 IgG 缀合的胶束相比,T-MP 在 LN 转移灶中积累更多。在手术切除原发性肿瘤后,用 T-MP 对转移性 LN 进行微创光热治疗,而不是对照胶束,延长了小鼠的存活时间。我们的研究结果首次表明,靶向小尺寸纳米粒子有可能为处理 LN 转移提供卓越的范例。延长老鼠的生存期。我们的研究结果首次表明,靶向小尺寸纳米粒子有可能为处理 LN 转移提供卓越的范例。延长老鼠的生存期。我们的研究结果首次表明,靶向小尺寸纳米粒子有可能为处理 LN 转移提供卓越的范例。

更新日期:2021-06-19
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