Hyperthermia Effect of Fe3O4 Nanoparticles Guided by Aptamer on 4T1 Breast Cancer Cells
Chen Enyuan1,2&, Jiang Zhengting3&, Ding Jiayi1, Kan Junnan1, Zu Hanyu1, Yan Peng3*
1(School of Medical Imaging, Binzhou Medical University, Yantai 264000, Shandong, China) 2(First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu, China) 3(School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, Shandong, China)
Abstract:Magnetic nanomaterials have been widely used in tumor imaging diagnosis and magnetic hyperthermia due to their unique magnetic properties. In this study, Fe3O4 nanoparticles were prepared by chemical coprecipitation method, and calreticulin receptor-targeted iron oxide nanoparticles (Fe3O4@Apt) were formed by coupling aptamer (Apt23) on the surface of the nanoparticles through an amide reaction. The hyperthermia effects of Fe3O4@Apt nanoparticles on breast cancer tumor cells (4T1) were investigated. The phase and crystal structure of Fe3O4 nanoparticles were analyzed by X-ray diffraction. The morphology, particle size, zeta potential and saturation magnetization of Fe3O4 nanoparticles before and after modification were characterized by transmission electron microscope, nanoparticle size analyzer and vibrating sample magnetometer, respectively. Functional groups on Fe3O4 nanoparticles, both before and post-modification, were analyzed through Fourier transform infrared spectroscopy. The targeting effect of Fe3O4 nanoparticles on 4T1 cells was determined by Prussian blue staining. Cell viability and proliferation of 4T1 cells and mouse embryonic fibroblasts (MEF) were detected by MTT assay. Under an alternating magnetic field (ACMF), the heating performance and in vitro magnetic hyperthermia effects of Fe3O4 nanoparticles before and after modification were measured. There were at least 3 replicates (n≥3) in all quantitative tests. Experimental results showed that the crystallization of Fe3O4 nanoparticles was good, and the morphology and magnetic properties of Fe3O4 nanoparticles did not change significantly before and after modification. The aptamer modification enhanced the surface electronegativity and increased the average particle size. The average particle sizes of Fe3O4 and Fe3O4@Apt were (9±4) and (18±5) nm, respectively. The zeta potentials were (-20.4±0.6) and (-27±0.4) mV, respectively. The absorption peak of Fe3O4@Apt nanoparticles at1 037 cm-1 indicated successful coupling with Apt23. Fe3O4 nanoparticles before and after modification could support the normal growth and proliferation of 4T1 and MEF cells. After 24 h incubation, there was no significant difference of the cells viability between Fe3O4@Apt nanoparticles and Fe3O4 nanoparticles at different concentrations (P>0.05). Under the ACMF, Fe3O4 nanoparticles exhibited effective heating capabilities before and after modification, and the cell proliferation rate in the targeted treatment group was lower than that in the control group (P<0.05). In conclusion, Fe3O4@Apt nanoparticles exhibited excellent targeting specificity toward breast cancer cell 4T1, and the magnetic hyperthermia effectively inhibited 4T1 cell proliferation in vitro.
陈恩远, 蒋政廷,丁佳怡, 阚俊楠, 祖涵瑜, 闫鹏. 核酸适配体介导的氧化铁纳米颗粒对4T1乳腺癌细胞的热疗效应[J]. 中国生物医学工程学报, 2024, 43(6): 712-719.
Chen Enyuan, Jiang Zhengting, Ding Jiayi, Kan Junnan, Zu Hanyu, Yan Peng. Hyperthermia Effect of Fe3O4 Nanoparticles Guided by Aptamer on 4T1 Breast Cancer Cells. Chinese Journal of Biomedical Engineering, 2024, 43(6): 712-719.
[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. [2] 甘凤娇. LncRNA BCAR4在局部晚期乳腺癌中的差异表达及与新辅助化疗疗效关联性研究[D]. 遵义:遵义医科大学, 2021. [3] Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways[J]. Cancer Cell, 2016, 29(4):452-463. [4] 秦娟,宋冬.乳腺癌不同时期治疗方式的研究进展[J].医学理论与实践,2022,35(12): 1001-7585. [5] Kok HP, Cressman ENK, Ceelen W, et al. Heating technology for malignant tumors: a review[J]. Int J Hyperthermia, 2020, 37(1):711-741. [6] Gilchrist RK, Medal R, Shorey WD, et al. Selective inductive heating of lymph nodes[J]. Ann Surg, 1957, 146(4):596-606. [7] 朱顺涛, 贺美娥, 杨广令, 等. 磁热治疗的最新研究进展[J]. 上海师范大学学报(自然科学版), 2019, 48(5):536-549. [8] 张宏波. 基于磁热耦合的磁流体热疗关键影响因素分析[D]. 郑州:郑州大学, 2021. [9] Wang Lijun, Zhou Hong, Wu Xue, et al. A novel colorimetric aptasensor for sensitive tetracycline detection based on the peroxidase-like activity of Fe3O4@Cu nanoparticles and "sandwich" oligonucleotide hybridization[J]. Mikrochim Acta, 2022, 189(3):86. [10] 杨丽媛, 陈华波, 周茜, 等. 磁性纳米四氧化三铁在肿瘤热疗领域中的研究进展[J]. 黑龙江医学, 2020, 44(5):698-701. [11] 姬文婵, 胡平, 汪小钰, 等. 影响磁性氧化铁纳米颗粒磁热疗加热效率的因素[J]. 材料科学与工程学报, 2022, 40(2):355-366. [12] 刘庆祖, 杨慧恺, 刘建恒, 等. 磁性纳米颗粒在肿瘤药物及肿瘤治疗中的研究进展[J]. 解放军医学院学报, 2020, 41(4):409-412. [13] Grauer O, Jaber M, Hess K, et al. Combined intracavitary thermotherapy with iron oxide nanoparticles and radiotherapy as local treatment modality in recurrent glioblastoma patients[J]. J Neurooncol, 2019, 141(1):83-94. [14] 胡润磊, 江洪, 马胜林. 磁流体热疗治疗肿瘤的研究进展[J]. 实用医学杂志, 2018, 34(7):1076-1079. [15] Kang SJ, Jeong HY, Kim MW, et al. Anti-EGFR lipid micellar nanoparticles co-encapsulating quantum dots and paclitaxel for tumor-targeted theranosis[J]. Nanoscale, 2018, 10(41):19338-19350. [16] 袁晨燕, 安艳丽, 王玲. 磁性纳米颗粒Fe3O4@PEI介导靶向自杀基因联合磁流体热疗对肝癌移植瘤的抑制作用[J]. 中国肿瘤生物治疗杂志, 2018, 25(9):913-919. [17] Jurek PM, Zabłocki K, Wa?ko U, et al. Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy[J]. Int J Nanomedicine, 2017, 12:2941-2950. [18] Sun Xiangyu, Liu Bing, Chen Xianli, et al. Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy[J]. J Mater Sci Mater Med, 2019, 30(7):76. [19] 岳东芳, 张迈鹤, 徐兆超, 等. 靶向乳腺癌的核酸适配体应用研究进展[J]. 大连医科大学学报, 2017, 39(2):181-188,192. [20] 孙淼, 杨歌, 赵毅, 等. 乳腺癌生物标志物钙网蛋白的核酸适配体筛选及血清检测和乳腺癌细胞识别[J]. 分析化学, 2020, 48(5):642-652. [21] 陈秀霞, 骆瑞珍, 门泉斌, 等. 钙网蛋白和驱动蛋白超家族蛋白5A在三阴性乳腺癌中的表达及意义[J]. 中国现代普通外科进展, 2021, 24(7):527-531. [22] 金明, 张志伟, 罗招阳. 钙网蛋白与肿瘤的相关研究进展[J]. 现代医药卫生, 2015, 31(21):3265-3268. [23] Patil S, Sandberg A, Heckert E, et al. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. [J] Biomaterials. 2007,28(31):4600-4607. [24] 王如平,王彦明,王泽虎,等.磁性纳米粒子在生物医学应用中的研究进展[J].山东化工,2022,51(6):97-98,102. [25] 陈小勇,刘晓丽,樊海明.磁性纳米材料的生物医学应用[J].物理,2020,49(6):381-389. [26] Xie Liqin, Jin Wanwan, Zuo Xxirui, et al. Construction of small-sized superparamagnetic Janus nanoparticles and their application in cancer combined chemotherapy and magnetic hyperthermia [J]. Biomater Sci, 2020 8(5):1431-1441. [27] Chandrasekharan P, Tay ZW, Hensley D, et al. Using magnetic particle imaging systems to localize and guide magnetic hyperthermia treatment: tracers, hardware, and future medical applications [J]. Theranostics. 2020,10(7):2965-2981. [28] 解丽芹,左喜瑞,张楠,等.磁性纳米颗粒的产热机制及在肿瘤热疗中的应用[J].中国生物医学工程学报,2021,40(5):608-619. [29] Kumar CS, Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery [J]. Adv Drug Deliv Rev, 2011,63(9):789-808. [30] Di Corato R, Espinosa A, Lartigue L, et al. Magnetic hyperthermia efficiency in the cellular environment for different nanoparticle designs[J]. Biomaterials, 2014,35(24):6400-6411. [31] Patade SR,Andhare DD,Somvanshi SB,et al.Self-heating evaluation of superparamagnetic MnFe2O4 nanoparticles formagnetic fluid hyperthermia application towards cancer treatment[J]. Ceramics International, 2020,46: 25576-25583. [32] Ota S,Yamada T,Takemura Y.Magnetization reversal and specific loss power of magnetic nanoparticles in cellular environment evaluated by AC hysteresis measurement[J]. Journal of Nanomaterials, 2015, 2015: 836761. [33] Gobbo OL, Sjaastad K, Radomski MW, et al. Magnetic nanoparticles in cancer theranostics [J]. Theranostics, 2015, 5(11):1249-1263. [34] Li Xuexin, Li Weiyuan, Wang Minan, et al. Magnetic nanoparticles for cancer theranostics: advances and prospects [J]. J Control Release, 2021,335:437-448. [35] 周灵丽,叶茂.核酸适配体介导的肿瘤免疫治疗研究进展[J].生物化学与生物物理进展,2022,49(6):1036-1044. [36] Zhou Jiehua, Rossi J. Aptamers as targeted therapeutics: current potential and challenges [J]. Nat Rev Drug Discov,2017,16(3):181-202.