Magnetic-Powered Janus Cell Robots Loaded with Oncolytic Adenovirus for Active and Targeted Virotherapy of Bladder Cancer.

Journal: Advanced materials (Deerfield Beach, Fla.)
PMID:

Abstract

A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe O nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.

Authors

  • Zhaoqing Cong
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Songsong Tang
    Department of NanoEngineering and Chemical Engineering Program, University of California San Diego, La Jolla, CA 92093, USA.
  • Leiming Xie
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Ming Yang
    Wuhan Institute for Food and Cosmetic Control, Wuhan 430014, China.
  • Yangyang Li
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Dongdong Lu
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Jiahong Li
    Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Qingxin Yang
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Qiwei Chen
    Institute of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
  • Zhiqiang Zhang
    Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
  • Xueji Zhang
    Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China. josephwang@ucsd.edu zhang@ucsd.edu zhangxueji@ustb.edu.cn.
  • Song Wu
    National Engineering Research Center for Big Data Technology and System, Services Computing Technology and System Lab, Cluster and Grid Computing Lab, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China.