Therapeutic-scale CAR-NK microrobots with programmable swarm navigation for targeted solid tumor therapy
An urgent requirement in chimeric antigen receptor (CAR) immune cell therapy [e.g., CAR–natural killer (NK) cells] for solid tumors is to engineer the cells for precise tumor targeting. Meanwhile, medical microrobots can be navigated toward specific target sites using external magnetic fields. Here, by bridging these approaches, we turn CAR-NK cells into magnetic biohybrid microrobots (CAR-NK microrobots) that achieve controllable long-distance targeted navigation at therapeutic doses (∼10 6 cells) in both murine and nonhuman primate animal models in vivo. CAR-NK microrobots are developed through genetic engineering with CAR structures and loading with magnetic nanoparticles for field-based navigation. Different magnetic field inputs reconfigure their swarms between vortex and ribbon modes, allowing dense aggregation for targeted navigation and further broad dispersion for large-area coverage. Using programmable magnetic fields, in vivo CAR-NK microrobot–based therapy is demonstrated for metastatic leptomeningeal carcinomatosis in brain’s cerebrospinal fluid space. After intrathecal injection, the microrobots are magnetically guided long distance through the spinal canal toward the brain in vortex mode and subsequently spread over the target site in ribbon mode, as visualized by real-time angiographic imaging in a nonhuman primate model, providing a proof-of-feasibility demonstration in a nonhuman primate anatomical setting.
Authors
- Xinjian Fan (ORCID: https://orcid.org/0000-0002-8854-1287)
- Yuxin Jia (ORCID: https://orcid.org/0000-0001-8808-2466)
- Lihai Zhang (ORCID: https://orcid.org/0000-0002-1282-992X)
- Zhiguang Wu (ORCID: https://orcid.org/0000-0002-0570-0757)
- Gongzi Zhang (ORCID: https://orcid.org/0000-0002-6955-7021)
- Mingtong Li (ORCID: https://orcid.org/0000-0002-1685-6052)
- Jie Zhao (ORCID: https://orcid.org/0000-0002-6086-9387)
- Hongri Gu (ORCID: https://orcid.org/0000-0002-6396-3408)
- Metin Sitti (ORCID: https://orcid.org/0000-0001-8249-3854)
- Hui Xie (ORCID: https://orcid.org/0000-0003-4299-2776)
- Hongda Wang (ORCID: https://orcid.org/0000-0003-0110-5624)
- Hongyue Zhang (ORCID: https://orcid.org/0000-0001-5354-3525)
- Ze‐sheng Li (ORCID: https://orcid.org/0000-0002-3392-8812)
- Ximing Sun (ORCID: https://orcid.org/0009-0003-3541-5281)
- Yalin Wang (ORCID: https://orcid.org/0000-0003-4095-1532)
- Yumeng Lu (ORCID: https://orcid.org/0009-0004-9229-1008)
- Jiawei Tian
- He Tan (ORCID: https://orcid.org/0009-0000-6046-2811)
- Jialin Wang (ORCID: https://orcid.org/0009-0000-0343-577X)
Institutions
- Koç University (TR)
- University of Alberta (CA)
- King's College London (GB)
- Hong Kong University of Science and Technology (HK)
- Harbin Institute of Technology (CN)
- Chinese PLA General Hospital (CN)
- Soochow University (CN)
- London Cancer (GB)
- Max Planck Institute for Intelligent Systems (DE)
- State Key Laboratory of Robotics and Systems (CN)
- Imperial College London (GB)
- University of Hong Kong (HK)
Publication Details
- Journal
- Science Advances
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1126/sciadv.aef9412
- Primary Topic
- Micro and Nano Robotics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- National Key Research and Development Program of China