Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington 99202, United States.
Department of Chemistry, Whitworth University, Spokane, Washington 99251, United States.
ACS Nano. 2023 Aug 22;17(16):15542-15555. doi: 10.1021/acsnano.3c02013. Epub 2023 Aug 14.
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 (10-10 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.
将抗癌药物有效递送至肿瘤微环境对于癌症治疗的成功至关重要,但前提是药物载体应克服肿瘤血管并具有高药物含量。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,并且中性粒细胞将靶向中性粒细胞的纳米颗粒(NPs)穿过肿瘤血屏障。结果表明,NPs 的肿瘤递药效率为 5% ID/g,且与粒径(30-200nm)和剂量(10-10 NPs)无关。为了通过中性粒细胞将抗癌剂有效递送至肿瘤中,我们制备了无载体紫杉醇纳米晶(PTX NC)。结果表明,PTX NC 的中性粒细胞摄取不会损害中性粒细胞对肿瘤的浸润,并且 PTX 从 PTX NC 在肿瘤中的可持续释放受到紫杉醇蛋白复合物的调节,从而提高了两种临床前模型中小鼠的存活率。我们的研究表明,通过中性粒细胞递送纳米晶药物是一种有前途的方法,可以有效治疗广泛的癌症,并且我们还确定了肿瘤中中性粒细胞释放药物的机制。
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