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NK-92细胞
BIOTECHNOLOGY PROGRESS · 2025 · IF 2.5

The combination of oleic acid, linoleic acid, palmitoleic acid, and α-linolenic acid promoted the expansion of NK-92 cells in vitro

Shumin Zhang,Huimin Huang,Jingwei Zhang,Yuanyuan Zhao,Wen-song Tan,Haibo Cai

Cell culture medium is an important factor affecting the expansion of NK cells in vitro. As an important component of cell culture medium, lipids participate in various complex physiological activities of cells and significantly affect the expansion of cells. Using NK-92 cells as a model, the lipid metabolism of NK cells in vitro was analyzed, and combined with the kinetic relationship between lipid metabolism and NK cell expansion. Four fatty acids, oleic acid, linoleic acid, palmitoleic acid, and α-linolenic acid, were preliminatively identified as the key lipid combinations. The combination was preliminarily verified on the self-developed serum-free medium. It was found that when the key lipid combination was added according to the concentration in the serum, NK-92 cells expansion reached 188.03 ± 33.34-folds, which was significantly higher than 105.28 ± 13.23-folds in the basic medium. Additionally, NK-92 cells expanded by adding key lipid combinations could maintain cell killing function. Overall, this research provides technical support for the development of NK cell serum-free medium.

CAS / MDL: 1634-04-4 67-56-1
研究领域: 免疫学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioresources and Bioprocessing · 2022 ·Vol. 9 ·期 1 ·1-11 · IF 4.983

A novel magnetically controlled bioreactor for ex vivo expansion of NK-92 cells

Liu Yangyang,Sun Qihao,Hao Mengyang,Tan Wen‑Song,Cai Haibo

The application of natural killer (NK) cells as potential antitumor effector cells appears to be valuable for immunotherapies. However, the clinical use of NK cells is limited because the technical difficulties associated with mass production NK cells at sufficiently high numbers represents a great challenge. Ex vivo expansion of NK cells is a key technology for cell therapy. Bioreactor systems can generate homogeneous culture condition and modulate the environmental and biochemical cues. In this study, a novel magnetically controlled bioreactor was developed for supporting NK cells ex vivo expansion. Using synthetic magnetic beads, the stirring device of the magnetically controlled bioreactor generated reduced shearing force. The intermittent magnetic field was applied for magnetic beads movement to homogenize the culture system. NK-92 cells were cultured in the magnetically controlled bioreactor and the expansion and function of expanded cells were investigated on day 8. The results showed that the expansion of NK-92 cells in the bioreactor was 67.71 ± 10.60-fold, which was significantly higher than that of the T25 culture flask (P < 0.05). Moreover, the proportions of CD3−CD56+ cells and cell killing activity of expanded cells in the bioreactor did not reveal any differences compared to T25 flasks. Taken together, this study demonstrated the possibility of magnetically controlled bioreactor as a potent strategy in NK cells production for facilitating cancer immunotherapy.

研究领域: 生物工程 · 免疫学 · 肿瘤学
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Nanoscale · 2021 ·Vol. 13 ·期 45 ·19109-19122 · IF 7.79

Surface specifically modified NK-92 cells with CD56 antibody conjugated superparamagnetic Fe3O4 nanoparticles for magnetic targeting immunotherapy of solid tumors

Songbo Zhao,Jiazhi Duan,Yalin Lou,Ruyun Gao,Shanshan Yang,Piming Wang,Chunhua Wang,Lin Han,Minghuan Li,Chunhong Ma,Xiaohong Liang,Hong Liu,Yuanhua Sang,Lifen Gao

Although there has been significant progress in the development of tumor immunotherapies, many challenges still exist for the treatment of solid tumors. Natural killer (NK) cells possess broad-spectrum cytotoxicity against tumors, but their limited migration and infiltration abilities restrict their application in solid tumor therapies. Here, we combined a facile and efficient magnetic-targeting strategy with NK cell-based therapy to develop a novel immunotherapy approach for treating solid tumors. Anti-CD56 antibodies were conjugated with Fe3O4 nanoparticles, which could specifically bind with NK-92 cells endowing them with a magnetic field driven targeting ability. These NK–Fe3O4 biohybrid nanoparticles were able to facilitate directional migration to the tumor site in vivo under external magnetic field guidance and efficiently inhibit tumor growth. These functionalized NK cells represent a novel approach for solid tumor therapy and may provide a promising modality for cancer interventions in the future.

研究领域: 生物技术 · 免疫学 · 癌症研究
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-13 · IF 10.6

NK-92 cells labeled with Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer

Lian Jingge,Li Meng,Duan Meng,Sun Yaqian,Wang Zilin,Guo Xinyu,Li Jingchao,Gao Guo,Li Kangan

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.

研究领域: 癌症治疗 · 免疫学 · 纳米技术 · 医学成像
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Acta Biomaterialia · 2022 · IF 10.633

Tumor microenvironment–responsive versatile “Trojan horse” theranostic nanoplatform for magnetic resonance imaging–guided multimodal synergistic antitumor treatment

Qingli Huang,Yuanjie Pan,Meng Wang,Zhaorong Liu,Huimin Chen,Jinglei Wang,Ziming Zhao,Yanzhuo Zhang

A natural killer (NK)-92 cell membrane-camouflaged mesoporous MnO 2 -enveloped [email protected] ( [email protected] @MnO 2 ) nanoparticles (denoted as APMN NPs)-based versatile biomimetic theranostic nanoplatform was developed for magnetic resonance (MR) imaging-guided multimodal synergistic antitumor treatments. In this core-shell nanostructure , an [email protected] core induced near-infrared (NIR)-activatable hyperthermal effects and nanozyme catalytic activity , while a mesoporous MnO 2 shell not only afforded a high drug-loading capability, tumor microenvironment (TME)-triggered MR imaging and drug release, but also endowed catalase-, glutathione peroxidase-, and Fenton-like activities. Furthermore, the NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein-mediated tumoral uptake property. The doxorubicin-loaded APMN (D-APMN) NPs exhibited TME-responsive drug release properties. Furthermore, the cellular uptake, in vivo MR imaging, and NIR thermal imaging confirmed the active tumor-targeting capability and TME-responsive MR imaging property of these biomimetic NPs. An antitumor efficacy test, histological analyses, and blood biochemical profiles suggested that the developed D-APMN NPs possessed a high antitumor activity and biosafety in tumor-bearing nude mice . Therefore, the developed APMN NPs held great potential as an intelligent and comprehensive theranostic nanoplatform for tumor-specific bioimaging and TME-responsive multimodality treatment based on photothermal therapy, chemodynamic therapy, and chemotherapy. Statement of significance Exploring intelligent and comprehensive theranostic nanoplatforms to integrate tumor-specific bioimaging and TME-responsive multimodal therapy effectively is a challenge. Herein, we successfully developed a new kind of NK-92 cell membrane-camouflaged mesoporous MnO 2 -enveloped [email protected] nanoparticles (APMN NPs)-based versatile biomimetic theranostic nanoplatform for the potential MR imaging-guided multimodal synergistic antitumor treatments. These NPs could integrate unique structural, optical, multiple-catalytic, paramagnetic, and biological merits of NK-92 cell membrane, [email protected] cores and mesoporous MnO 2 shell in a single nanoplatform. The NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein–mediated tumoral uptake property. The new information obtained from this study may be beneficial to promote the development of novel TME-responsive versatile “Trojan horse” theranostic nanoplatforms for efficient MR imaging-guided multimodal synergistic treatment.

研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 材料科学 · 诊疗学
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