具有仿生特性的纳米机器人的位点选择性超级组装，使其能够在硬化的肿瘤基质中深入穿透。
Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma.
发表日期：2023 Aug 02
作者：
Miao Yan, Qing Chen, Tianyi Liu, Xiaofeng Li, Peng Pei, Lei Zhou, Shan Zhou, Runhao Zhang, Kang Liang, Jian Dong, Xunbin Wei, Jinqiang Wang, Osamu Terasaki, Pu Chen, Zhen Gu, Libo Jiang, Biao Kong
来源：
PHYSICAL THERAPY & REHABILITATION JOURNAL
摘要：
化疗仍然是三阴性乳腺癌（TNBC）的首选治疗方法。然而，目前基于纳米载体系统的肿瘤渗透能力有限和细胞内吸收效率低，阻碍了抗癌药物进入具有密集基质的TNBC，从而极大地限制了临床治疗效果，特别对于TNBC的骨转移。在本研究中，通过选择性超组装策略设计了仿生头/中空尾纳米机器人。我们展示了纳米机器人通过有效重塑致密的肿瘤基质微环境（TSM）以实现深层肿瘤渗透。此外，纳米机器人的自运动能力和针状头部显著促进了细胞界面吸收效率、经血管外渗和肿瘤内渗透。这些纳米机器人将深层肿瘤渗透、主动细胞内吸收、近红外（NIR）光响应释放和光热疗法能力集成到单个纳米器件中，有效抑制了TNBC的骨转移女性小鼠模型中的肿瘤生长，并在三个不同的皮下肿瘤模型中显示了强大的抗肿瘤功效。© 2023. 作者。
Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.© 2023. The Author(s).