Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma
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
Abstract
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.