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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 20, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-022-01480-z
Popis: 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.
Databáze: Directory of Open Access Journals
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