4.8 Article

Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 31, Pages 12025-12037

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c03071

Keywords

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Funding

  1. Social Development Project of Jiangsu Natural Science Foundation [BE2019744]
  2. Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
  3. Qinglan Project Foundation of Colleges and Universities of Jiangsu Province
  4. Priority Academic Program Development of Jiangsu Higher Education Institution

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The study demonstrated that nitric oxide (NO)-driven nanomotors with drug-loading capabilities can significantly improve the infiltration ability of T cells in tumor tissues by promoting normalization of tumor vasculature system and degradation of extracellular matrix (ECM). The combination of motility and physiological function of nanomotors provides a promising design idea for future immunotherapy of various diseases.
The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.

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