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中华介入放射学电子杂志 ›› 2024, Vol. 12 ›› Issue (01) : 51 -57. doi: 10.3877/cma.j.issn.2095-5782.2024.01.009

基础研究

铁铜基纳米材料在肝癌微波增敏治疗中的应用效果
罗汐1, 田伟1, 孙汉垚1, 路尚于1, 施海彬1,()   
  1. 1. 210029 江苏南京,南京医科大学第一附属医院介入放射科
  • 收稿日期:2023-11-24 出版日期:2024-02-25
  • 通信作者: 施海彬
  • 基金资助:
    国家自然科学基金(81901855)

Iron-copper based nanomaterials for microwave sensitization treatment of hepatocellular carcinoma

Xi Luo1, Wei Tian1, Hanyao Sun1, Shangyu Lu1, Haibin Shi1,()   

  1. 1. Department of Interventional Radiology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Nanjing 210029, China
  • Received:2023-11-24 Published:2024-02-25
  • Corresponding author: Haibin Shi
引用本文:

罗汐, 田伟, 孙汉垚, 路尚于, 施海彬. 铁铜基纳米材料在肝癌微波增敏治疗中的应用效果[J]. 中华介入放射学电子杂志, 2024, 12(01): 51-57.

Xi Luo, Wei Tian, Hanyao Sun, Shangyu Lu, Haibin Shi. Iron-copper based nanomaterials for microwave sensitization treatment of hepatocellular carcinoma[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2024, 12(01): 51-57.

目的

探讨铁铜基金属有机框架(Fe-Cu MOFs)纳米材料的制备、物化表征并联合微波消融在肝癌的治疗疗效。

方法

采用水热方法合成Fe-Cu MOFs纳米材料,观察其理化特征并通过测定不同浓度(0、2、6、10 mg/mL)的体外微波升温效果对微波增敏能力进行评估。此外,在细胞水平上评估其生物相容性,并探究与微波消融联合治疗对细胞增殖的抑制效果。随后通过构建H22肝癌小鼠皮下瘤模型,以评估Fe-Cu MOFs联合MW治疗后对肿瘤生长的抑制效果。

结果

成功构建具有立面体结构的Fe-Cu MOFs纳米材料,粒径为(182.28 ± 0.79)nm。在微波照射下,随微波辐射时间及纳米材料浓度的提高,升温也随之增强。Fe-Cu MOFs联合MW对肿瘤细胞增殖有显著的抑制作用,同时体内实验证实,Fe-Cu MOFs联合MW组小鼠肿瘤部位温度明显高于MW组,并且联合治疗组的小鼠肿瘤体积得到有效抑制。

结论

Fe-Cu MOFs铁铜基金属有机框架纳米材料具有良好的微波增敏性能,可有效提高微波消融在肝癌的治疗疗效。

Objective

To investigate the preparation, physicochemical characterization of iron-copper-based metal-organic frameworks (Fe-Cu MOFs) nanomaterials combined with microwave ablation in treating Hepatocellular Carcinoma.

Methods

Fe-Cu MOFs nanomaterials were synthesized by hydrothermal method, their physicochemical characteristics were observed, and the microwave sensitization ability was evaluated by measuring the microwave heating effect of different concentrations (0, 2, 6, 10 mg/mL)in vitro. In addition, biocompatibility was evaluated at the cellular level, and the inhibitory effect of combined therapy with microwave ablation on cell proliferation was explored. Subsequently, a subcutaneous tumor model in H22 Hepatocellular Carcinoma mice was established to evaluate the inhibitory effect of Fe-Cu MOFs combined with MW on tumor growth.

Results

Fe-Cu MOFs nanomaterials with a faceted structure and a particle size of (182.28 ± 0.79) nm was successfully synthesized. The heating effect under microwave irradiation increased with the duration and concentration of the nanomaterials. Fe-Cu MOFs combined with microwave irradiation notably suppressed tumor cell proliferation. In vivo studies showed that mice treated with Fe-Cu MOFs and microwaves exhibited higher tumor site temperatures and significantly reduced tumor volumes compared to microwave-only treatment.

Conclusion

Fe-Cu MOFs nanomaterials have good microwave sensitization properties, which can effectively improve the therapeutic effect of microwave ablation in Hepatocellular Carcinoma.

图1 Fe-Cu MOFs纳米颗粒的理化特征1A:Fe-Cu MOFs透射电镜图像,标尺为500 nm(左上角:50 μm);1B:Fe-Cu MOFs的Zeta电位,n = 3,数据采用平均值±标准差;1C:Fe-Cu MOFs的水合粒径分布。
图2 Fe-Cu MOFs纳米颗粒的微波热转换性能2A:不同浓度Fe-Cu MOFs的升温热像图;2B:不同浓度Fe-Cu MOFs的升温曲线;2C:升温温差柱状图。
图3 Fe-Cu MOFs纳米颗粒细胞毒性及体外联合微波治疗疗效3A:不同浓度Fe-Cu MOFs与HepG2、Hepa1-6共孵育24 h后的细胞活性情况;3B:活死染色检测微波与特定浓度Fe-Cu MOFs联合微波的细胞杀伤作用,标尺:50 μm;3C:流式细胞凋亡检测Fe-Cu MOFs联合微波的治疗效果。
图4 Fe-Cu MOFs磁共振成像能力4A:不同浓度的Fe-Cu MOFs的T1加权磁共振成像;4B:注射Fe-Cu MOFs前H22肿瘤小鼠的活体T1加权磁共振成像(冠状面);4C:注射Fe-Cu MOFs后H22肿瘤小鼠的活体T1加权磁共振成像(冠状面)。
图5 Fe-Cu MOFs纳米颗粒联合微波在体内治疗疗效5A:治疗结束时微波组和Fe-Cu MOFs +微波组小鼠的红外热像图;5B:不同组别荷瘤小鼠治疗结束后肿瘤照片;5C:不同组别荷瘤小鼠的平均肿瘤生长曲线(与对照组比较,*P < 0.05,****P < 0.05);5D为Fe-Cu MOFs +微波组的小鼠治愈图。
图6 荷瘤小鼠治疗后各器官(心、肝、脾、肺、肾)HE染色,标尺为100 μm
[1]
Chen Z, Xie H, Hu M, et al. Recent progress in treatment of hepatocellular carcinoma[J]. Am J Cancer Res, 2020, 10(9):2993-3036.
[2]
Pinter M, Pinato D J, Ramadori P, et al. NASH and hepatocellular carcinoma: immunology and immunotherapy[J]. Clin Cancer Res, 2023, 29(3): 513-520.
[3]
徐克, 邵海波. 肝癌介入治疗新进展[J]. 肝癌电子杂志, 2020, 7(3): 2-6.
[4]
Leuchte K, Staib E, Thelen M, et al. Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2021, 70(4): 893-907.
[5]
Imajo K, Ogawa Y, Yoneda M, et al. A review of conventional and newer generation microwave ablation systems for hepatocellular carcinoma[J]. Journal of Medical Ultrasonics, 2020, 47(2): 265-277.
[6]
Liu X, Zhu X, Qi X, et al. Co-administration of iRGD with sorafenib-loaded iron-based metal-organic framework as a targeted ferroptosis agent for liver cancer therapy[J]. Int J Nanomedicine, 2021, 16: 1037-1050.
[7]
Ma X, Ren X, Guo X, et al. Multifunctional iron-based Metal-Organic framework as biodegradable nanozyme for microwave enhancing dynamic therapy[J]. Biomaterials, 2019, 214: 119223.
[8]
唐顺松, 付长慧, 黄忠兵, 等. 微波增敏的mPEG-PLGA栓塞微球治疗原发性肝癌的研究[J]. 影像科学与光化学, 2018, 36(2): 130-136.
[9]
Cao XJ, Wei Y, Zhao ZL, et al. Efficacy and safety of microwave ablation for cervical metastatic lymph nodes arising post resection of papillary thyroid carcinoma: a retrospective study[J]. Int J Hyperthermia, 2020, 37(1): 450-455.
[10]
Zhang Y, Guo L, Kong F, et al. Nanobiotechnology-enabled energy utilization elevation for augmenting minimally-invasive and noninvasive oncology thermal ablation[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2021, 13(6): e1733.
[11]
Qi J, Li W, Lu K, et al. pH and thermal dual-sensitive nanoparticle-mediated synergistic antitumor effect of immunotherapy and microwave thermotherapy[J]. Nano Lett, 2019, 19(8): 4949-4959.
[12]
Zhang D, Zhang Y, Luo Y, et al. Perfluoropentane/apatinib-encapsulated metal–organic framework nanoparticles enhanced the microwave ablation of hepatocellular carcinoma[J]. Nanoscale Adv,2023, 5(18): 4892-4900.
[13]
Li R, Tian Y, Zhu B, et al. Graphene-containing metal–organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma[J]. Nanoscale Adv, 2022, 4(5): 1308-1317.
[14]
Wang L, Xu Y, Liu C, et al. Copper-doped MOF-based nanocomposite for GSH depleted chemo/photothermal/chemodynamic combination therapy[J]. Chem Eng J, 2022, 438: 135567.
[15]
Huang DQ, Mathurin P, Cortez-Pinto H, et al. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(1): 37.
[16]
Chen S, Zeng X, Su T, et al. Combinatory local ablation and immunotherapies for hepatocellular carcinoma: rationale, efficacy, and perspective[J]. Front Immunol, 2022, 13: 1033000.
[17]
Wicks JS, Dale BS, Ruffolo L, et al. Comparable and complimentary modalities for treatment of small-sized HCC: surgical resection, radiofrequency ablation, and microwave ablation[J]. J Clin Med, 2023, 12(15): 5006.
[18]
Min H, Wang J, Qi Y, et al. Biomimetic metal-organic framework nanoparticles for cooperative combination of antiangiogenesis and photodynamic therapy for enhanced efficacy[J]. Adv Mater, 2019, 31(15): 1808200.
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