Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA.
Sci Adv. 2020 Mar 25;6(13):eaay1601. doi: 10.1126/sciadv.aay1601. eCollection 2020 Mar.
The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand ("active targeting") is superior to its unlabeled counterpart ("passive targeting"). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8 T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.
在体系统递送后影响纳米颗粒命运的因素仍然是一个研究热点。特别感兴趣的是，用癌症特异性抗体配体进行标记（“主动靶向”）是否优于未标记的配体（“被动靶向”）。我们使用三种免疫变异型小鼠的乳腺癌模型，证明了肿瘤内抗体标记纳米颗粒的保留取决于肿瘤相关树突状细胞、中性粒细胞、单核细胞和巨噬细胞，而不是抗体-抗原相互作用。系统暴露于这两种纳米颗粒类型都会引发免疫反应，导致 CD8 T 细胞浸润和肿瘤生长延迟，而与抗体治疗活性无关。这些结果表明，系统暴露于纳米颗粒可以诱导抗肿瘤免疫反应，而不需要治疗有效载荷。我们得出结论，宿主的免疫状态和实体瘤的微环境是癌症纳米医学研究中的关键变量，纳米颗粒技术可能具有癌症免疫治疗的潜力。
