In Vivo Monocyte/Macrophage-Hitchhiked Intratumoral Accumulation of Nanomedicines for Enhanced Tumor Therapy
In Vivo Monocyte/Macrophage-Hitchhiked Intratumoral Accumulation of Nanomedicines for Enhanced Tumor Therapy
复制标题
体内单核细胞/巨噬细胞搭便车在瘤内积累纳米药物以增强肿瘤治疗
DOI：
10.1021/jacs.9b11046
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发表时间：
2020
影响因子：
15
通讯作者：
Tan Weihong
中科院分区：
文献类型：
--
作者：
Zheng Liyan;Hu Xiaoxiao;Wu Hui;Mo Liuting;Xie Sitao;Li Jin;Peng Cheng;Xu Shujuan;Qiu Liping;Tan Weihong
实体瘤的内部区域被发现是高压、低氧和免疫抑制的，为肿瘤的侵袭和转移提供了温床。虽然纳米药物在肿瘤内的积累与免疫调节相结合将显著提高治疗效果，但这种潜力受到肿瘤体积压缩环境和明显异质性的挑战。通过使用凋亡小体(AB)作为载体，我们开发了一种有效的、通用的肿瘤内纳米药物传递系统，以实现肿瘤的长期缓解。我们的结果表明，AB包裹的纳米药物(以CpG免疫佐剂修饰的金银纳米棒为模型)静脉注射后，可以被炎性Ly-6C+单核细胞特异性吞噬，然后通过其自然的肿瘤归巢倾向主动渗透到肿瘤中心。结合AB促进的肿瘤内蓄积、基于纳米棒的光热效应和CpG促进的免疫刺激作用，这种细胞介导的递送系统不仅可以有效地消融原发肿瘤，而且可以诱导强大的免疫力，防止肿瘤的转移和复发。
The inner region of solid tumors is found to be high-pressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor bulk. By using an apoptotic body (AB) as the carrier, we develop an effective and universal intratumoral nanomedicine delivery system for the long-lasting remission of tumors. Our results show that the AB-encapsulated nanomedicine (using CpG immunoadjuvant-modified gold–silver nanorods as a model), after intravenous injection, can be specifically phagocytosed by inflammatory Ly-6C+monocytes, which then actively infiltrate the tumor center via their natural tumor-homing tendency. With the integration of AB-facilitated intratumoral accumulation, the nanorod-based photothermal effect, and CpG-promoted immunostimulation, this cell-mediated delivery system can not only efficiently ablate primary tumors but also elicit a potent immunity to prevent tumors from metastasizing and recurring.