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Neutrophils, as "Trojan horses", participate in the delivery of therapeutical PLGA nanoparticles into a tumor based on the chemotactic effect.
Drug Delivery ( IF 6 ) Pub Date : 2019-12-09 , DOI: 10.1080/10717544.2019.1701141
Jifu Hao 1 , Junlan Chen 2 , Meixiang Wang 3, 4 , Jing Zhao 1 , Jianze Wang 1 , Xingrong Wang 1 , Yuhong Li 2 , Hua Tang 3, 4
Affiliation  

Inspired by the fact that leukocytes have innate phagocytic functions and oriented migration capabilities in response to chemoattractants, we have unveiled that endogenous neutrophils as "Trojan horses", participate in the delivery of nanoparticles in an "in vivo self-armed assembly" manner. Neutrophils were the main population to preferentially sequester the intravenous administrated nanoparticles with an average size of 260 nm. The pre-implantation of CXCL1-laden hydrogels could trigger and induce a targeted signal to attract an influx of neutrophils carrying the therapeutic goods to the desired position. In mouse models of melanoma, the combinatorial regimen of using the PLGA nanoparticles with the CXCL1 hydrogels exhibited superior tumor inhibition capability. This work leveraged the natural phagocytosis of neutrophile and the chemotactic effect of chemokines for targeted delivery. We believe this strategy will improve the therapeutic efficiency of nanoparticle-based delivery systems, especially when the chemokines are implanted at sites of surgical tumor removal, during cancer treatment at the clinic.

中文翻译:

中性粒细胞,作为“特洛伊木马”,基于趋化作用,参与将治疗性PLGA纳米粒子递送到肿瘤中。

受白细胞具有天生的吞噬功能和针对趋化因子的定向迁移能力的启发,我们揭示了内源性中性粒细胞(“特洛伊木马”)以“体内自我武装组装”的方式参与纳米颗粒的递送。中性粒细胞是优先隔离平均粒径为260 nm的静脉注射纳米颗粒的主要人群。载有CXCL1的水凝胶的预植入可触发并诱导靶向信号,以吸引携带治疗性药物的嗜中性粒细胞大量涌入所需位置。在黑色素瘤的小鼠模型中,将PLGA纳米颗粒与CXCL1水凝胶一起使用的组合方案显示出优异的肿瘤抑制能力。这项工作利用嗜中性粒细胞的自然吞噬作用和趋化因子的趋化作用进行靶向递送。我们相信这种策略将提高基于纳米颗粒的递送系统的治疗效率,尤其是在临床癌症治疗期间将趋化因子植入手术切除肿瘤的部位时。
更新日期:2020-04-20
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