切换至 "中华医学电子期刊资源库"
高级检索
中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2025, Vol. 15 ›› Issue (05) : 312 -320. doi: 10.3877/cma.j.issn.2095-1221.2025.05.008

综述

纳米材料在增强自然杀伤细胞靶向治疗中的应用研究进展
骆鑫源1, 王元昕2, 周远畅1, 陈可蕙1, 李泽歆1, 张基旺1, 张磊升2,†(), 郑朝晖1,†()   
  1. 1362000　泉州，福建医科大学附属第二医院耳鼻咽喉科
    2250031　济南，山东第二医科大学附属济南市第四人民医院科创中心（山东省医药卫生血液生态与生物智造重点实验室&济南市医学细胞组织工程重点实验室）
  • 收稿日期:2025-09-01 出版日期:2025-10-01
  • 通信作者: 张磊升, 郑朝晖
  • 基金资助:
    国家自然科学基金(82460027); 福建省自然科学基金(2023J01722); 福建省卫健委科技基金(2023CXA033); 泉州市科技局高层次人才基金(2022C033R); 山东省医药卫生科技项目面上项目(202402050122); 济南市卫生健康委员会科技发展计划项目(2024301008、2025202005); 济南市科技计划临床医学科技创新项目(202430055); 山东省自然科学基金面上项目(ZR2025MS1382); 山东省政府非教育系统公派出国留学项目(202403001)

Progress in nanoparticle application for improving natural killer cell-based targeted therapy

Xinyuan Luo1, Yuanxin Wang2, Yuanchang Zhou1, Kehui Chen1, Zexin Li1, Jiwang Zhang1, Leisheng Zhang2,†(), Chaohui Zheng1,†()   

  1. 1Department of Otolaryngology, The Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, China
    2Science and Technology Innovation Center, Shandong Provincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, Jinan Key Laboratory of Medical Cell Bioengineering, The Fourth People's Hospital of Jinan Affiliated to Shandong Second Medical University, Jinan 250031, China
  • Received:2025-09-01 Published:2025-10-01
  • Corresponding author: Leisheng Zhang, Chaohui Zheng
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

骆鑫源, 王元昕, 周远畅, 陈可蕙, 李泽歆, 张基旺, 张磊升, 郑朝晖. 纳米材料在增强自然杀伤细胞靶向治疗中的应用研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 312-320.

Xinyuan Luo, Yuanxin Wang, Yuanchang Zhou, Kehui Chen, Zexin Li, Jiwang Zhang, Leisheng Zhang, Chaohui Zheng. Progress in nanoparticle application for improving natural killer cell-based targeted therapy[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2025, 15(05): 312-320.

自然杀伤（NK）细胞是一类先天性淋巴细胞，它们无需预先致敏即可快速激活多种信号通路，直接杀伤病毒感染的细胞或肿瘤细胞。由于T淋巴细胞的局限性及NK细胞的独特属性，基于NK细胞的免疫疗法在一定程度上优于T细胞免疫疗法，但仍存在一些局限。例如，NK细胞在肿瘤微环境（TME）中的功能沉默、治疗效果有限以及治疗成本高昂。纳米材料是一类粒径在1 ~ 100nm范围内的材料，通过改变其形状、尺寸、疏水性、表面修饰物等，可以实现药物、细胞因子、RNA等的靶向递送，进而定向改造靶组织的微环境或者靶细胞的生物特性，增强免疫治疗的效果。纳米技术的最新进展，为基于NK细胞的免疫疗法优化提供了新的应用方向。本文系统地概述了NK细胞的免疫治疗、增强免疫治疗的纳米技术，以及利用纳米颗粒改善NK细胞靶向治疗的最新进展。

关键词: NK细胞, 免疫治疗, 纳米技术, 靶向治疗

Natural killer (NK) cells, a subset of innate lymphocytes, rapidly activate multiple signaling pathways without prior sensitization to directly eliminate virus-infected cells or tumor cells. Due to the limitations of T lymphocytes and the unique traits of NK cells, NK cell-based immunotherapies reveal multifaceted advantages over T cell-based ones to some extent. However, they still have certain limitations, such as NK cell silence in tumor microenvironment (TME), limited therapeutic effect, and high treatment costs. Nanomaterials are materials with a diameter ranging from 1 nm to 100 nm. By precisely manipulating the physical and chemical properties (e.g, shape, size, hydrophobicity, and surface modifications), nanomaterials can be engineered to achieve targeted delivery of therapeutic agents (e.g., drugs, cytokines, and RNAs). This capability enables precise manipulation of the microenvironment in target tissues or specific modulation of cellular behaviors, thereby enhancing the efficacy of immunotherapy strategies. The state-of-the-art progress in nanoparticles has supplied new applications for NK cell-based immunotherapies. Herein, we outline the immunotherapy of NK cells, nanotechnology that enhances immunotherapy, and recent advances in nanoparticles for facilitating the targeted therapy by NK cells.

Key words: NK cells, Immunotherapy, Nanotechnology, Targeted therapy
图1 NK细胞的四种主要来源注：NK-92细胞为人恶性非霍奇金淋巴瘤患者的自然杀伤细胞；KHYG-1细胞为人自然杀伤细胞淋巴瘤细胞。（此图使用Adobe illustrator软件自制）
图2 NK细胞的代表性活化性与抑制性受体注：此图使用Adobe illustrator软件自制
图3 肿瘤微环境注：肿瘤微环境通过以下机制抑制NK细胞活性：（1）分泌免疫抑制因子；（2）富集免疫抑制细胞；（3）分泌趋化因子。肿瘤细胞通过分泌免疫抑制因子（如吲哚胺2,3-双加氧酶、转化生长因子-β等）直接抑制NK细胞功能；同时通过分泌趋化因子促进免疫抑制细胞（如肿瘤相关巨噬细胞、髓源性抑制细胞、调节性T细胞等）在肿瘤部位的聚集；此外，肿瘤还可直接诱导免疫抑制细胞的富集，进而抑制NK细胞活性。（此图使用Adobe illustrator软件自制）
图4 纳米颗粒增强NK细胞功能的策略注：（a）纳米颗粒辅助免疫调节以增强自然杀伤细胞活性；（b）纳米颗粒增强自然杀伤细胞的归巢能力；（c）纳米颗粒递送RNA干扰（RNAi）以增强自然杀伤细胞活性；（d）纳米颗粒用于自然杀伤细胞的基因修饰。（此图使用Adobe illustrator软件自制）
表1 关于增强NK细胞靶向治疗效果的纳米颗粒的综合信息详述
纳米材料 辅助方式 机制 特点 优势 缺陷
抗GD2抗体偶联金纳米颗粒[99] 无 刺激NK细胞以杀伤GD2阳性肿瘤，并特异性增强计算机断层扫描成像的对比度 该策略适用于神经母细胞瘤、黑色素瘤及其他潜在的GD2阳性恶性肿瘤 良好的生物相容性、可功能化修饰能力及放射性标记潜力 不可生物降解性及潜在毒性
磁性纳米颗粒[103,104] 无 磁性纳米颗粒可在外部磁场引导下定向至体内特定部位 该物质易在肝脏、脾脏及淋巴结中积累 可生物降解性、良好的生物相容性、可功能化修饰性及放射性标记潜力 神经毒性
纳米氧化石墨烯[106] 无 无细胞可溶性试剂，其利用受体纳米簇激活免疫细胞 增强NK细胞的脱颗粒能力及细胞因子（如IFN-γ）的分泌水平 在不与靶表面结合的前提下分离活化NK细胞 制备工艺复杂
靶向性NK-92细胞[109] MRI引导的聚焦超声联合微泡超声造影剂 MRI引导的聚焦超声联合微泡超声造影剂技术，可实现靶向性NK-92细胞向脑肿瘤细胞的递送 穿透血脑屏障 生物安全性与特异性细胞毒性 细胞需求量大且成本高昂
氧化铁纳米颗粒[110] MRI引导导管 采用MRI引导导管灌注氧化铁纳米颗粒，用以标记NK细胞并靶向肝肿瘤 该技术可增强NK细胞的归巢效应，并有望作为一种无创工具用于预测治疗反应 可实时可视化、归巢效应显著且具有重要早期生物标志物特征 铁毒性
1
Murugan D, Murugesan V, Panchapakesan B, et al. Nanoparticle enhancement of natural killer (NK) cell-based immunotherapy[J]. Cancers(Basel), 2022, 14(21):5438.
2
Liu S, Galat V, Galat Y, et al. NK cell-based cancer immunotherapy:from basic biology to clinical development[J]. J Hematol Oncol, 2021, 14(1):7.
3
Dai Z, Zhang J, Wu Q, et al. Intestinal microbiota:a new force in cancer immunotherapy[J]. Cell Commun Signal, 2020, 18(1):90.
4
陈琼, 吴卓龙, 黄吉炜. 免疫治疗在局部进展期肾癌围手术期治疗中的应用进展[J/OL]. 中华腔镜泌尿外科杂志（电子版）, 2025, 19(4): 418-422.
5
June CH, Sadelain M. Chimeric antigen receptor therapy[J]. N Engl J Med, 2018, 379(1):64-73.
6
Gun SY, Lee SWL, Sieow JL, et al. Targeting immune cells for cancer therapy[J]. Redox Biol, 2019, 25:101174.
7
Mukhametshin SA, Gilyazova EM, Davletshin DR, et al. Allogeneic NKG2D CAR-T cell therapy: a promising approach for treating solid tumors[J]. Biomedicines, 2025, 13(9):2314.
8
Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy[J]. Nat Rev Clin Oncol, 2019, 16(6):372-385.
9
Ershova A, Goldaeva A, Staliarova A, et al. Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology[J]. Front Immunol, 2025, 16:1592377.
10
Grefe M, Trujillo-Ocampo A, Clinton J, et al. Cord blood-derived iNK T cells as a platform for allogeneic CAR T cell therapy[J]. Front Immunol, 2025, 16:1621260.
11
Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy-assessment and management of toxicities[J]. Nat Rev Clin Oncol, 2017, 15(1):47-62.
12
Molfetta R, Quatrini L, Santoni A, et al. Regulation of NKG2D-dependent NK cell functions:the yin and the yang of receptor endocytosis[J]. Int J Mol Sci, 2017, 18(8):1677.
13
Rascle P, Woolley G, Jost S, et al. NK cell education:physiological and pathological influences[J]. Front Immunol, 2023, 14:1087155.
14
Freud AG, Mundy-Bosse BL, Yu J, et al. The broad spectrum of human natural killer cell diversity[J]. Immunity, 2017, 47(5):820-833.
15
Nath PR, Maclean M, Nagarajan V, et al. Single-cell profiling identifies a CD8bright CD244bright natural killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy[J]. Nat Commun, 2024, 15(1):6443.
16
Luo N, Chen C, Zhou W, et al. Natural killer Cell-mediated antitumor immunity:molecular mechanisms and clinical applications[J]. MedComm (2020), 2025, 6(9):e70387.
17
Chen Y, Lu D, Churov A, Fu R. Research progress on NK cell receptors and their signaling pathways[J]. Mediators Inflamm, 2020, 2020:6437057.
18
Lindsay RS, Melssen MM, Stasiak K, et al. NK cells reduce anergic T cell development in early-stage tumors by promoting myeloid cell maturation[J]. Front Oncol, 2022, 12:1058894.
19
Myers JA, Schirm D, Bendzick L, et al. Balanced engagement of activating and inhibitory receptors mitigates human NK cell exhaustion[J]. JCI Insight, 2022, 7(15):e150079.
20
Liu E, Marin D, Banerjee P, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors[J]. N Engl J Med, 2020, 382(6):545-553.
21
Arapović M, Brizić I, Popović B, et al. Intrinsic contribution of perforin to NK-cell homeostasis during mouse cytomegalovirus infection[J]. Front Immunol, 2016, 7:133.
22
Khanal S, Baer A, Hossain MK, et al. Soluble factors released by peripheral blood-derived CAR-NK cells cause bystander myeloid cell activation[J]. Front Immunol, 2024, 15:1519415.
23
Gao H, Liu M, Zhang Y, et al. Multifaceted characterization of the biological and transcriptomic signatures of natural killer cells derived from cord blood and placental blood[J]. Cancer Cell Int, 2022, 22(1): 291.
24
Xie B, Zhang L, Gao J, et al. Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood[J]. Am J Cancer Res, 2023, 13(5):2087-2103.
25
McLaughlin Q, Sojka DK, Kennedy K, et al. Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances[J]. J Exp Clin Cancer Res, 2025, 44(1):251.
26
Qin Y, Cui Q, Sun G, et al. Developing enhanced immunotherapy using NKG2A knockout human pluripotent stem cell-derived NK cells[J]. Cell Rep, 2024, 43(11):114867.
27
Terrén I, Orrantia A, Vitallé J, et al. NK cell metabolism and tumor microenvironment[J]. Front Immunol, 2019, 10:2278.
28
Jia H, Yang H, Xiong H, et al. NK cell exhaustion in the tumor microenvironment[J]. Front Immunol, 2023, 14:1303605.
29
Stankovic B, Bjørhovde HAK, Skarshaug R, et al. Immune cell composition in human non-small cell lung cancer[J]. Front Immunol, 2019, 9:3101.
30
Chen P, Gao J, Feng J, et al. The application of iPSCs in tumour immunotherapy[J]. Expert Rev Mol Med, 2025, 27:e26.
31
Cheng M, Chen Y, Xiao W, et al. NK cell-based immunotherapy for malignant diseases[J]. Cell Mol Immunol, 2013, 10(3):230-252.
32
Han B, Song Y, Park J, et al. Nanomaterials to improve cancer immunotherapy based on ex vivo engineered T cells and NK cells[J]. J Control Release, 2022, 343:379-391.
33
Jeanbart L, Swartz MA. Engineering opportunities in cancer immunotherapy[J]. Proc Natl Acad Sci U S A, 2015, 112(47):14467-14472.
34
Davila ML, Kloss CC, Gunset G, et al. CD19 CAR-targeted T cells induce long-term remission and B cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia[J]. PLoS One, 2013, 8(4):e61338.
35
Miller JS, Rooney CM, Curtsinger J, et al. Expansion and homing of adoptively transferred human natural killer cells in immunodeficient mice varies with product preparation and in vivo cytokine administration: implications for clinical therapy[J]. Biol Blood Marrow Transplant, 2014, 20(8):1252-1257.
36
Jaiswal SR, Zaman S, Nedunchezhian M, et al. CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease:A pilot study[J]. Cytotherapy, 2017, 19(4):531-542.
37
Ikeda H. T-cell adoptive immunotherapy using tumor-infiltrating T cells and genetically engineered TCR-T cells[J]. Int Immunol, 2016, 28(7):349-353.
38
Bahramloo M, Shahabi SA, Kalarestaghi H, et al. CAR-NK cell therapy in AML: current treatment, challenges, and advantage[J]. Biomed Pharmacother, 2024, 177:117024.
39
Kazemi T, Younesi V, Jadidi-Niaragh F, et al. Immunotherapeutic approaches for cancer therapy: an updated review[J]. Artif Cells Nanomed Biotechnol, 2016, 44(3):769-779.
40
Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer:harnessing the T cell response[J]. Nat Rev Immunol, 2012, 12(4):269-281.
41
Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy [J]. Nat Rev Drug Discov. 2020, 19(3):200-218.
42
Lee DA, Denman CJ, Rondon G, et al. Haploidentical natural killer cells infused before allogeneic stem cell transplantation for myeloid malignancies: a phase I trial[J]. Biol Blood Marrow Transplant, 2016, 22(7):1290-1298.
43
Matosevic S. Viral and nonviral engineering of natural killer cells as emerging adoptive cancer immunotherapies[J]. J Immunol Res, 2018, 2018:4054815.
44
Miller JS, Rooney CM, Curtsinger J, et al. Expansion and homing of adoptively transferred human natural killer cells in immunodeficient mice varies with product preparation and in vivo cytokine administration: implications for clinical therapy[J]. Biol Blood Marrow Transplant, 2014, 20(8):1252-1257.
45
Li Y, Sun R. Tumor immunotherapy: new aspects of natural killer cells[J]. Chin J Cancer Res, 2018, 30(2):173-196.
46
Blunt MD, Vallejo Pulido A, Fisher JG, et al. KIR2DS2 expression identifies NK cells with enhanced anticancer activity[J]. J Immunol, 2022, 209(2):379-390.
47
Hiura S, Kuwasaki Y, Nishikawa Y, et al. Selective agonists of KIR and NKG2A to evade missing self response of natural killer cells[J]. Sci Rep, 2025, 15(1):33550.
48
Peng P, Lou Y, Wang S, et al. Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy[J]. J Immunother Cancer, 2022, 10(12):e005769.
49
Suck G, Branch DR, Smyth MJ, et al. KHYG-1, a model for the study of enhanced natural killer cell cytotoxicity[J]. Exp Hematol, 2005, 33(10):1160-1171.
50
Kim Y, Lee DY, Choi JU, et al. Optimized conditions for gene transduction into primary immune cells using viral vectors[J]. Sci Rep, 2023, 13(1):12365.
51
Caligiuri MA. Human natural killer cells[J]. Blood, 2008, 112(3):461-469.
52
Tomaz D, Pereira PM, Guerra N, et al. Nanoscale colocalization of NK cell activating and inhibitory receptors controls signal integration[J]. Front Immunol, 2022, 13:868496.
53
Dhar P, Wu JD. NKG2D and its ligands in cancer[J]. Curr Opin Immunol, 2018, 51:55-61.
54
Wu L, Zhang C, Zhang J. HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway[J]. Cell Mol Immunol, 2011, 8(5):433-440.
55
Bjorkstrom NK, Ljunggren HG, Michaelsson J. Emerging insights into natural killer cells in human peripheral tissues[J]. Nat Rev Immunol, 2016, 16(5):310-320.
56
Sun C, Sun H, Zhang C, et al. NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma[J]. Cell Mol Immunol, 2014, 12(3):292-302.
57
Habif G, Crinier A, André P, et al. Targeting natural killer cells in solid tumors[J]. Cell Mol Immunol, 2019, 16(5):415-422.
58
Zhang C, Hu Y, Shi C. Targeting natural killer cells for tumor immunotherapy[J]. Front Immunol, 2020, 11:60.
59
Castriconi R, Cantoni C, Della Chiesa M, et al. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells[J]. Proc Natl Acad Sci U S A, 2003, 100(7):4120-4125.
60
Cekic C, Day YJ, Sag D, et al. Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment[J]. Cancer Res, 2014, 74(24):7250-7259.
61
Li H, Han Y, Guo Q, et al. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1[J]. J Immunol, 2009, 182(1):240-249.
62
Nayyar G, Chu Y, Cairo MS. Overcoming resistance to natural killer cell based immunotherapies for solid tumors[J]. Front Oncol, 2019, 9:51.
63
Kim KS, Kim DH, Kim DH. Recent advances to augment NK cell cancer immunotherapy using nanoparticles[J]. Pharmaceutics, 2021, 13(4):525.
64
Shin MH, Kim J, Lim SA, et al. NK cell-based immunotherapies in cancer[J]. Immune Netw, 2020, 20(2):e14.
65
Liu S, Galat V, Galat Y, et al. NK cell-based cancer immunotherapy: from basic biology to clinical development[J]. J Hematol Oncol, 2021, 14(1):7.
66
Yamanaka S. Pluripotent stem cell-based cell therapy-promise and challenges[J]. Cell Stem Cell, 2020, 27(4):523-531.
67
Bleeker EA, de Jong WH, Geertsma RE, et al. Considerations on the EU definition of a nanomaterial:science to support policy making[J]. Regul Toxicol Pharmacol, 2013, 65(1):119-125.
68
Feng X, Xu W, Li Z, et al. Immunomodulatory nanosystems[J]. Adv Sci, 2019, 6(17):1900101.
69
Shukla S, Steinmetz NF. Emerging nanotechnologies for cancer immunotherapy[J]. Exp Biol Med, 2016, 241(10):1116-1126.
70
Wei P, Moodera JS. One compound with two distinct topological states[J]. Nat Mater, 2020, 19(5):481-482.
71
Irvine DJ, Dane EL. Enhancing cancer immunotherapy with nanomedicine[J]. Nat Rev Immunol, 2020, 20(5):321-334.
72
Le Saux G, Schvartzman M. Advanced materials and devices for the regulation and study of NK cells[J]. Int J Mol Sci, 2019, 20(3):646.
73
Owensiii D, Peppas N. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles[J]. Int J Pharm, 2006, 307(1):93-102.
74
Toy R, Peiris PM, Ghaghada KB, et al. Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey of nanoparticles[J]. Nanomedicine (Lond), 2014, 9(1):121-134.
75
Yoo JW, Mitragotri S. Polymer particles that switch shape in response to a stimulus[J]. Proc Natl Acad Sci U S A, 2010, 107(25):11205-11210.
76
Lasic DD, Papahadjopoulos D. Liposomes revisited[J]. Science, 1995, 267(5202):1275-1276.
77
Delcassian D, Depoil D, Rudnicka D, et al. Nanoscale ligand spacing influences receptor triggering in T cells and NK cells[J]. Nano Lett, 2013, 13(1):5608-5614.
78
Mikelez-Alonso I, Magadán S, González-Fernández á, et al. Natural killer (NK) cell-based immunotherapies and the many faces of NK cell memory: a look into how nanoparticles enhance NK cell activity[J]. Adv Drug Deliv Rev, 2021, 176:113860.
79
Daka A, Peer D. RNAi-based nanomedicines for targeted personalized therapy[J]. Adv Drug Deliv Rev, 2012, 64(13):1508-1521.
80
Mittler RS, Foell J, McCausland M, et al. Anti-CD137 antibodies in the treatment of autoimmune disease and Cancer[J]. Immunol Res, 2004, 29(1-3):197-208.
81
Cheuk ATC, Mufti GJ, Guinn B-a. Role of 4-1BB:4-1BB ligand in cancer immunotherapy[J]. Cancer Gene Ther, 2003, 11(3):215-226.
82
Liu Z, Jiang W, Nam J, et al. Immunomodulating nanomedicine for cancer therapy[J]. Nano Lett, 2018, 18(11):6655-6659.
83
Liu C, Lai H, Chen T. Boosting natural killer cell-B based cancer immunotherapy with selenocystine/transforming growth factor-beta inhibitor-encapsulated nanoemulsion[J]. ACS Nano, 2020, 14(9):11067-11082.
84
Tan L, Han S, Ding S, et al. Chitosan nanoparticle-based delivery of fused NKG2D&ndash: IL-21 gene suppresses colon cancer growth in mice[J]. Int J Nanomedicine, 2017, 12:3095-3107.
85
Pan J, Xu Y, Wu Q, et al. Mild magnetic hyperthermia-activated innate immunity for liver cancer therapy[J]. J Am Chem Soc, 2021, 143(21):8116-8128.
86
Zhang SC, Hu ZQ, Long JH, et al. Clinical implications of tumor-infiltrating immune cells in breast cancer[J]. J Cancer, 2019, 10(24): 6175-6184.
87
Ran Gh, Lin Yq, Tian L, et al. Natural killer cell homing and trafficking in tissues and tumors:from biology to application[J]. Signal Transduct Target Ther, 2022, 7(1):205.
88
Park W, Gordon AC, Cho S, et al. Immunomodulatory magnetic microspheres for augmenting tumor-specific infiltration of natural killer (NK) cells[J]. ACS Appl Mater Interfaces, 2017, 9(16):13819-13824.
89
Burga RA, Khan DH, Agrawal N, et al. Designing magnetically responsive biohybrids composed of cord blood-derived natural killer cells and iron oxide nanoparticles[J]. Bioconjug Chem, 2019, 30(30):552-560.
90
Gasparri AM, Sacchi A, Basso V, et al. Boosting interleukin-12 antitumor activity and synergism with immunotherapy by targeted delivery with isoDGR-Tagged nanogold[J]. Small. 2019, 15(45): e1903462
91
Monty MA, Islam MA, Nan X, et al. Emerging role of RNA interference in immune cells engineering and its therapeutic synergism in immunotherapy[J]. Br J Pharmacol, 2021, 178(8):1741-1755.
92
Biber G, Sabag B, Raiff A, et al. Modulation of intrinsic inhibitory checkpoints using nano-carriers to unleash NK cell activity[J]. EMBO Mol Med, 2022, 14(1):e14073.
93
Riggan L, Shah S, O'Sullivan TE. Arrested development: suppression of NK cell function in the tumor microenvironment[J]. Clin Transl Immunology, 2021, 10(1):e1238.
94
Melaiu O, Lucarini V, Cifaldi L, et al. Influence of the tumor microenvironment on NK cell function in solid tumors[J]. Front Immunol, 2020, 10:3038.
95
Hu Z, Xu X, Wei H. The adverse impact of tumor microenvironment on NK-cell[J]. Front Immunol, 2021, 12:633361.
96
Buabeid MA, Arafa EA, Murtaza G. Emerging prospects for nanoparticle-enabled cancer immunotherapy[J]. J Immunol Res, 2020, 2020:9624532.
97
Kim KS, Han JH, Park JH, et al. Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics[J]. Biomaterials, 2019, 221:119418.
98
Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer[J]. Nat Rev Drug Discov, 2008, 7(9):771-782.
99
Baiu DC, Artz NS, McElreath MR, et al. High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles[J]. Nanomedicine, 2015, 10(19):2973-2988.
100
Ahmed M, Cheung NK. Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy[J]. FEBS Letters, 2014, 588(2):288-297.
101
Jiao P, Otto M, Geng Q, et al. Enhancing both CT imaging and natural killer cell-mediated cancer cell killing by a GD2-targeting nanoconstruct[J]. J Mater Chem B, 2016, 4(3):513-520.
102
Zheng K, Setyawati MI, Leong DT, et al. Antimicrobial Gold Nanoclusters[J]. ACS Nano, 2017, 11(7):6904-6910.
103
Foy SP, Manthe RL, Foy ST, et al. Optical imaging and magnetic field targeting of magnetic nanoparticles in tumors[J]. ACS Nano, 2010, 4(9):5217-5224.
104
Nowak-Jary J, Machnicka B. In vivo biodistribution and clearance of magnetic iron oxide nanoparticles for medical applications[J]. Int J Nanomedicine, 2023, 18:4067-4100.
105
Wu L, Zhang F, Wei Z, et al. Magnetic delivery of Fe3O4@polydopamine nanoparticle-loaded natural killer cells suggest a promising anticancer treatment[J]. Biomater Sci, 2018, 6(10):2714-2725.
106
Loftus C, Saeed M, Davis DM, et al. Activation of human natural killer cells by graphene oxide-templated antibody nanoclusters[J]. Nano Lett, 2018, 18(5):3282-3289.
107
Baek A, Baek YM, et al. Polyethylene glycol-engrafted graphene oxide as biocompatible materials for peptide nucleic acid delivery into cells[J]. Bioconjug Chem, 2018, 29(2):528-537.
108
Grasso G, Torregrossa F, Noto M, et al. MR-guided focused ultrasound-induced blood-brain barrier opening for brain metastasis: a review[J]. Neurosurg Focus, 2023, 55(2):E11.
109
Alkins R, Burgess A, Kerbel R, et al. Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival[J]. Neuro Oncol, 2016, 18(7):974-981.
110
Su Z, Wang X, Zheng L, et al. MRI-guided interventional natural killer cell delivery for liver tumor treatment[J]. Cancer Med, 2018, 7(5):1860-1869.
111
Sheu AY, Zhang Z, Omary RA, et al. MRI-monitored transcatheter intra-arterial delivery of SPIO-labeled natural killer cells to hepatocellular carcinoma[J]. Invest Radiol, 2013, 48(6):492-499.
112
Srivastava S, Lundqvist A, Childs RW. Natural killer cell immunotherapy for cancer: a new hope[J]. Cytotherapy, 2008, 10(8): 775-783.
113
Shah A, Dobrovolskaia MA. Immunological effects of iron oxide nanoparticles and iron-based complex drug formulations: therapeutic benefits, toxicity, mechanistic insights, and translational considerations[J]. Nanomedicine, 2018, 14(3):977-990.
114
Zhang X, Xu F, Hu X, et al. Zinc mitigates copper toxicity in Crassostrea gigas by regulating metal homeostasis, oxidative stress, and immune responses[J]. Mar Environ Res, 2025, 211:107393.
115
Lee AR, Lee SJ, Lee M, et al. Editor's Highlight: a genome-wide screening of target genes against silver nanoparticles in fission yeast[J]. Toxicol Sci, 2018, 161(1):171-185.
116
Pandey A, Mishra AK. Immunomodulation, toxicity, and therapeutic potential of nanoparticles[J]. BioTech (Basel), 2022, 11(3):42.
117
Müller L, Steiner SK, Rodriguez-Lorenzo L, et al. Exposure to silver nanoparticles affects viability and function of natural killer cells, mostly via the release of ions[J]. Cell Biol Toxicol, 2018, 34(3):167-176.
118
Müller L, Steiner SK, Rodriguez-Lorenzo L, et al. Exposure to silver nanoparticles affects viability and function of natural killer cells, mostly via the release of ions[J]. Cell Biol Toxicol, 2018, 34(3):167-176.
119
Wang P, Lu YQ. Ferroptosis: a critical moderator in the life cycle of immune cells[J]. Front Immunol, 2022, 13:877634.
120
Tang H, Xu M, Luo J, et al. Liver toxicity assessments in rats following sub-chronic oral exposure to copper nanoparticles[J]. Environ Sci Eur, 2019, 31:30.
121
Yao Y, Zang Y, Qu J, et al. The toxicity of metallic nanoparticles on liver: the subcellular damages, mechanisms, and outcomes[J]. Int J Nanomedicine, 2019, 14:8787-8804.
122
Jindal A, Sarkar S, Alam A. Nanomaterials-mediated immunomodulation for cancer therapeutics[J]. Front Chem, 2021, 9: 629635.
[1] 赵诗迪, 杨姣, 周妍, 范园, 杨谨. CDK4/6抑制剂在激素受体阳性晚期乳腺癌一线治疗中的挑战及进展后策略[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 257-266.
[2] 周润楷, 蔡锦锋, 王法芝, 于洋, 温玉刚. 磷脂酰肌醇-3-激酶/蛋白激酶B通路在结直肠癌细胞程序性死亡中的作用机制及靶向治疗研究进展[J/OL]. 中华普通外科学文献(电子版), 2025, 19(04): 280-288.
[3] 钱龙, 蔡大明, 王行舟, 艾世超, 胡琼源, 孙锋, 宋鹏, 王峰, 王萌, 陆晓峰, 朱欢欢, 沈晓菲, 管文贤. 局部不可切除胃癌转化治疗（联合免疫治疗）后淋巴结转移的相关危险因素分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(06): 624-627.
[4] 王思竣, 王琼, 李珂雨, 袁新普, 张硕珉, 马睿, 谢天宇, 张朝军. 胃上部癌新辅助化疗联合免疫治疗后实施近端胃切除术的临床疗效分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(06): 637-641.
[5] 高峰, 郝少龙, 孙浩, 韩威. 三级淋巴结构在胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(05): 570-573.
[6] 廖志成, 朱黎, 曾志宇. 广东省医学会泌尿外科疑难病例多学科会诊（第27期）——晚期肾癌[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(05): 669-676.
[7] 李才坤, 张又红, 肖斌彬, 温盼, 刘醒, 刘志栋, 周剑辉, 温春玲, 叶劲, 严恒琛. 三维斑点追踪在肺癌患者免疫治疗后左心房功能损害评价的应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 821-823.
[8] 刘丽辉, 白玉新, 张进, 冯巍, 黄琰琰, 邹梦斯, 刘彩红. 血清生物标志物联合检测对支气管哮喘患儿生物靶向治疗效果的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 796-801.
[9] 张宇涵, 吴添庆, 高汶卿, 郑梽楷, 贺珉睿, 周仲国. 不可切除性肝内胆管癌不同治疗方式疗效和安全性的Meta分析[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 939-947.
[10] 许侨东, 马志延, 冯庚壬, 钟海彬, 刘坚锐, 古松钢. 肝肺多发性原发性癌转化治疗后行腹腔镜肝右前叶切除术一例（附视频）[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 973-976.
[11] 胡铭语, 李敬东, 肖雨竹, 黄杰. 初始不可切除肝癌患者转化治疗序贯手术的临床疗效分析[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(05): 754-760.
[12] 赵南, 张明凯, Bhargava Divija, 赵世光, 张大明. 结直肠癌脑转移的临床特征与治疗策略进展[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(05): 427-435.
[13] 李鑫睿, 江明珠, 时萍, 牟洪宾. 线粒体稳态在慢性肾脏病发病机制中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2025, 14(05): 276-287.
[14] 王春茂, 韩鸣, 王子彤. 局限期小细胞肺癌新辅助治疗后完全病理学缓解五例[J/OL]. 中华临床医师杂志(电子版), 2025, 19(07): 550-554.
[15] 侯雨函, 姜福金, 王苏贵. 膀胱癌免疫治疗的研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(06): 471-475.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号

AI
小
编
AI小编
你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？