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Copper Sulfide Nanoparticle‐Redirected Macrophages for Adoptive Transfer Therapy of Melanoma
Author(s) -
Xu Jiaojiao,
Zheng Binbin,
Zhang Sihang,
Liao Xueling,
Tong Qinli,
Wei Guoguang,
Yu Sheng,
Chen Gaoxian,
Wu Aihua,
Gao Shuai,
Qian Yuyi,
Xiao Zeyu,
Lu Wei
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202008022
Subject(s) - adoptive cell transfer , cancer research , tumor microenvironment , melanoma , materials science , macrophage , intracellular , immune system , immunology , biology , microbiology and biotechnology , t cell , in vitro , biochemistry
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‐κB activation. Moreover, the copper sulfide nanoparticle‐stimulated BMDMs (CuS‐MΦ) reduce the expression of programmed death‐1 (PD‐1) and exhibit enhanced phagocytic and digestive ability. Intratumoral transfer of CuS‐MΦ 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.