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Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2020-11-16 , DOI: 10.1038/s41551-020-00644-2
Zongmin Zhao 1, 2 , Anvay Ukidve 1, 2 , Vinu Krishnan 1, 2 , Alexandra Fehnel 1 , Daniel C Pan 1, 2 , Yongsheng Gao 1, 2 , Jayoung Kim 1, 2 , Michael A Evans 1, 2 , Abhirup Mandal 1, 2 , Junling Guo 2 , Vladimir R Muzykantov 3 , Samir Mitragotri 1, 2
Affiliation  

Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.



中文翻译:

通过红细胞锚定趋化因子封装纳米颗粒在肺转移瘤中的优先积累来抑制全身肿瘤

原发性肿瘤的免疫抑制微环境和更深层次的肿瘤内细胞更难接近,阻碍了引发针对原发性肿瘤的免疫反应。然而,转移性肿瘤细胞暴露于高灌注和免疫活性的器官,例如肺。在这里,通过利用静脉注射红细胞与肺部转移的优先共定位,我们证明用非共价锚定在注射红细胞表面的趋化因子封装纳米颗粒进行治疗可在小鼠模型中产生局部和全身肿瘤抑制的肺转移。这种红细胞锚定的全身免疫疗法使效应免疫细胞浸润到肺部,无需外源抗原即可进行原位免疫,抑制肺转移的进展,并显着延长动物的存活时间和抑制远处肿瘤生长的全身免疫。再次挑战后的​​肿瘤。红细胞介导的全身免疫疗法可能代表一种通用且有效的癌症疫苗接种策略。

更新日期:2020-11-17
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