期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 11, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202008022
关键词
adoptive cell therapy; copper sulfide nanoparticle; macrophage; reactive oxygen species; solid tumor
类别
资金
- National Natural Science Foundation of China [81991493, 91859110, 21874092]
- Program of Shanghai Academic Research Leader [19XD1420200]
The study presents a novel adoptive macrophage therapy using copper sulfide nanoparticles to induce ROS production and inhibit tumor growth, improve the tumor microenvironment, elicit systemic antitumor immunity, thus prolonging the survival time of tumor patients.
Adoptive cell therapy (ACT) has achieved landmark advances in treating cancer in clinic. Recent advances in ACT of macrophages engineered to express chimeric antigen receptors (CARs) have shown effectiveness in treating solid tumors. However, the CAR-macrophage therapy is dependent on tumor antigen recognition and gene editing methods. Herein, an adoptive macrophage therapy is presented through copper sulfide nanoparticle-regulation that exhibits substantial antitumor effect in melanoma-bearing mice, without the need for tumor antigen repertoire. Bone marrow derived macrophages (BMDMs) incubated with the nanoparticles promote the cellular production of reactive oxygen species (ROS) through dynamin-related protein 1 (Drp1)-mediated mitochodrial fission. The high intracellular ROS level directs BMDMs polarization toward M1 phenotype by classical IKK-dependent NF-kappa B activation. Moreover, the copper sulfide nanoparticle-stimulated BMDMs (CuS-M phi) reduce the expression of programmed death-1 (PD-1) and exhibit enhanced phagocytic and digestive ability. Intratumoral transfer of CuS-M phi significantly prolongs the median survival time of the tumor-bearing mice, remodels the tumor microenvironment, and elicits systemic antitumor immunity. These results suggest a cancer therapeutic approach of adoptively transferred macrophages through the induction of intracellular ROS with nanomaterials.
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