Neutrophil-Mediated Delivery of Nanocrystal Drugs via Photoinduced Inflammation Enhances Cancer Therapy.
Neutrophil-Mediated Delivery of Nanocrystal Drugs via Photoinduced Inflammation Enhances Cancer Therapy.
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DOI：
10.1021/acsnano.3c02013
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发表时间：
2023-08
期刊：
影响因子：
17.1
通讯作者：
Yu-Yan Su;Jin Gao;Xinyue Dong;K. Wheeler;Zhenjia Wang
中科院分区：
文献类型：
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作者：
Yu-Yan Su;Jin Gao;Xinyue Dong;K. Wheeler;Zhenjia Wang
将抗癌药物有效地递送到肿瘤微环境中对于癌症治疗的成功至关重要，但药物载体应克服肿瘤血管并具有高药物含量是先决条件。在这里，我们发现光诱导的炎症反应导致中性粒细胞迁移到肿瘤微环境中，中性粒细胞将嗜中性粒细胞靶向的纳米颗粒（NP）转运穿过肿瘤血液屏障。结果表明，纳米粒的肿瘤递送效率为5%ID/g，并且它们与粒径（30-200 nm）和它们的剂量（108-1011个纳米粒）无关。为了通过嗜中性粒细胞有效地将抗癌剂递送到肿瘤中，我们制造了无载体紫杉醇纳米晶体（PTX NC）。结果表明，中性粒细胞摄取PTX NC并不损害中性粒细胞肿瘤浸润，并且紫杉醇蛋白复合物调节肿瘤中PTX NC的PTX持续释放，从而改善了两种临床前模型中小鼠的存活率。我们的研究表明，通过嗜中性粒细胞递送抗肿瘤药物是一种有效治疗多种癌症的有前途的方法，我们还确定了肿瘤中嗜中性粒细胞释放药物的机制。
The efficient delivery of anticancer agents into tumor microenvironments is critical for the success of cancer therapies, but it is a prerequisite that drug carriers should overcome tumor vasculature and possess high drug contents. Here, we found that photoinduced inflammation response caused the migration of neutrophils into tumor microenvironments and neutrophils transported neutrophil-targeted nanoparticles (NPs) across the tumor blood barrier. The results showed that tumor delivery efficiencies of NPs were 5% ID/g, and they were independent of particle sizes (30-200 nm) and their doses (108-1011 NPs). To efficiently deliver anticancer agents into tumors via neutrophils, we fabricated carrier-free paclitaxel nanocrystals (PTX NC). The results showed that neutrophil uptake of PTX NC did not impair neutrophil tumor infiltration, and the sustainable release of PTX from PTX NC in tumors was regulated by paclitaxel protein complexes, thus improving the mouse survival in two preclinical models. Our studies demonstrate that delivery of nanocrystal drugs via neutrophils is a promising method to effectively treat a wide range of cancers, and we have also identified a mechanism of drug release from neutrophils in tumors.