Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance.
Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance.
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DOI：
10.1021/acsnano.5b05999
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发表时间：
2016-01-26
期刊：
影响因子：
17.1
通讯作者：
DeSimone JM
中科院分区：
文献类型：
--
作者：
Kai MP;Brighton HE;Fromen CA;Shen TW;Luft JC;Luft YE;Keeler AW;Robbins GR;Ting JP;Zamboni WC;Bear JE;DeSimone JM
长循环纳米颗粒对于增加肿瘤积聚以提供治疗功效至关重要。虽然已知肿瘤的存在可以改变免疫系统，但很少有研究探索这种对纳米颗粒循环的影响。在这份报告中，我们展示了肿瘤的存在如何改变局部和全局免疫系统，从而显著增加颗粒清除率。我们发现，肿瘤的存在显著增加了PRINT水凝胶纳米颗粒从循环中的清除，导致肝脏和脾脏中的积累增加，这是由于M2样巨噬细胞的增加。我们的研究结果强调需要更好地了解免疫状态和纳米颗粒清除之间的相互作用，并表明需要进一步考虑免疫功能才能在临床前和临床纳米颗粒研究中取得成功。
Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.