Journal of Nanobiotechnology (Jun 2022)

Dual-binding nanoparticles improve the killing effect of T cells on solid tumor

  • Zhenyu Luo,
  • Lihua Luo,
  • Yichao Lu,
  • Chunqi Zhu,
  • Bing Qin,
  • Mengshi Jiang,
  • Xiang Li,
  • Yingying Shi,
  • Junlei Zhang,
  • Yu Liu,
  • Xinyu Shan,
  • Hang Yin,
  • Guannan Guan,
  • Yongzhong Du,
  • Ningtao Cheng,
  • Jian You

DOI
https://doi.org/10.1186/s12951-022-01480-z
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

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Abstract Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.

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