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.

中文翻译：

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纳米粒子与免疫细胞的相互作用在乳腺癌模型中占主导地位，并诱导T细胞介导的肿瘤抑制。

全身递送后影响体内纳米颗粒命运的因素仍然是人们关注的领域。特别令人感兴趣的是用癌症特异性抗体配体（“主动靶向”）标记是否优于未标记的对应物（“被动靶向”）。使用小鼠三种免疫变体中的乳腺癌模型，我们证明抗体标记的纳米颗粒在肿瘤内的保留是由肿瘤相关的树突状细胞，嗜中性粒细胞，单核细胞和巨噬细胞决定的，而不是由抗体-抗原相互作用决定的。全身性地暴露于任一纳米颗粒类型均会导致免疫反应，导致CD8 + T细胞浸润和肿瘤生长延迟，而与抗体的治疗活性无关。这些结果表明，通过全身性暴露于纳米颗粒可以诱导抗肿瘤免疫反应，而无需治疗有效载荷。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的关键变量，纳米颗粒技术可能具有癌症免疫疗法的潜力。