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刺激响应性共聚物修饰金纳米棒的制备及其抗肿瘤性能

郭敏 侯光晖 胥伟军 钱军民

郭敏, 侯光晖, 胥伟军, 钱军民. 刺激响应性共聚物修饰金纳米棒的制备及其抗肿瘤性能[J]. 功能高分子学报, 2022, 35(1): 44-53. doi: 10.14133/j.cnki.1008-9357.20210323001
引用本文: 郭敏, 侯光晖, 胥伟军, 钱军民. 刺激响应性共聚物修饰金纳米棒的制备及其抗肿瘤性能[J]. 功能高分子学报, 2022, 35(1): 44-53. doi: 10.14133/j.cnki.1008-9357.20210323001
GUO Min, HOU Guanghui, XU Weijun, QIAN Junmin. Preparation of Stimulus-Responsive Copolymer-Decorated Gold Nanorods and Their Anti-Tumor Effect[J]. Journal of Functional Polymers, 2022, 35(1): 44-53. doi: 10.14133/j.cnki.1008-9357.20210323001
Citation: GUO Min, HOU Guanghui, XU Weijun, QIAN Junmin. Preparation of Stimulus-Responsive Copolymer-Decorated Gold Nanorods and Their Anti-Tumor Effect[J]. Journal of Functional Polymers, 2022, 35(1): 44-53. doi: 10.14133/j.cnki.1008-9357.20210323001

刺激响应性共聚物修饰金纳米棒的制备及其抗肿瘤性能

doi: 10.14133/j.cnki.1008-9357.20210323001
基金项目: 国家自然科学基金(82073309);陕西省重点研发计划(2020SF-033,2020GY-290)
详细信息
    作者简介:

    郭敏:郭 敏(1996—),女,宁夏中卫人,硕士生,从事多功能纳米颗粒抗癌的研究。E-mail:1348092181@qq.com

    通讯作者:

    钱军民,E-mail:jmqian@mail.xjtu.edu.cn

  • 中图分类号: TB34

Preparation of Stimulus-Responsive Copolymer-Decorated Gold Nanorods and Their Anti-Tumor Effect

  • 摘要: 以1-叔丁氧基羰基-2-丙烯酰肼(Boc-AH)、N-(3,4-二羟基苯乙基)丙烯酰胺(DA)和聚乙二醇甲醚丙烯酸酯(mPEGA)为单体,利用可逆加成-断裂链转移聚合法制备了嵌段共聚物聚丙烯酰肼-聚N-(3,4-二羟基苯乙基)丙烯酰胺-聚单甲氧基聚乙二醇丙烯酸酯(PAH-b-PAD-b-PmPEGA,缩写为HDP),该共聚物经酚羟基偶联于金纳米棒(GNR)表面,酰肼基团与阿霉素(DOX)中羰基形成酸敏感的腙键从而实现药物装载,构建了光热-化疗联合治疗的纳米体系(HDP-GNR-DOX)。利用紫外-可见(UV-Vis)吸收光谱和溶液颜色变化检测GNR的悬浮稳定性。利用透射电镜、流式细胞术和激光共聚焦显微镜研究了纳米药物被细胞摄取及细胞内分布情况。利用MTT法评估HDP-GNR-DOX介导的光热-化疗联合治疗效果。利用活/死细胞检验方法进一步分析了纳米药物对细胞的杀伤效果。结果表明,该纳米体系载药率高达8.1%,具有优异的光热性能和pH响应性药物释放性能。细胞实验表明,该纳米体系可被人乳腺癌细胞(MCF-7)有效摄取,具有光热-化疗协同杀伤肿瘤细胞的功效。

     

  • 图  1  HDP-GNR-DOX 纳米药物的制备及其在细胞中的运输示意图

    Figure  1.  Schemic diagram of preparation and intracellular transport of HDP-GNR-DOX nanodrug

    图  2  样品的1H-NMR谱图

    Figure  2.  1H-NMR spectra of samples

    图  3  样品的(a) FT-IR谱图、(b) UV-Vis吸收光谱、(c)流体力学粒径和(d) Zeta电位

    Figure  3.  (a) FT-IR spectra, (b) UV-Vis spectra, (c) hydrodynamic sizes and (d) Zeta potentials of samples

    图  4  (a) CTAB-GNR和(b) HDP-GNR的TEM图像

    Figure  4.  TEM images of (a) CTAB-GNR and (b) HDP-GNR

    图  5  (a)CTAB-GNR和HDP-GNR-DOX在PBS和水中的UV-Vis吸收光谱和照片;(b)HDP-GNR-DOX释放DOX的动力学曲线

    Figure  5.  (a) UV-Vis spectra and photographs of CTAB-GNR and HDP-GNR-DOX in water and PBS;(b) Release profiles of DOX from HDP-GNR-DOX

    图  6  (a)样品的光热性能;(b) HDP-GNR-DOX浓度和(c) NIR光功率对光热效果的影响;(d) HDP-GNR-DOX光热性能的稳定性

    Figure  6.  (a) Photothermal performance of samples; Effects of (b) HDP-GNR-DOX concentration and (c) NIR power on photothermal performance; (d)Photothermal stability of HDP-GNR-DOX

    图  7  HDP-GNR-DOX处理MCF-7的(a)TEM图像和(b)细胞内荧光强度

    Figure  7.  (a) TEM images and (b) fluorescence intensity of MCF-7 treated with HDP-GNR-DOX

    图  8  (a)HDP-GNR-DOX和(b)游离DOX处理MCF-7不同时间后DOX的细胞内分布

    Figure  8.  Intracellular distribution of DOX in MCF-7 incubated with (a) HDP-GNR-DOX and (b) free DOX

    图  9  (a) HDP-GNR的细胞毒性;(b)不同制剂处理MCF-7后的细胞活力;(c)光热化疗(HDP-GNR-DOX + NIR)联合疗效与单纯PTT(HDP-GNR + NIR)和单纯化疗(HDP-GNR-DOX)叠加疗效的比较

    Figure  9.  (a) Cytotoxicity of HDP-GNR; (b) Viability of MCF-7 treated with different formulations; (c) Comparison of combined efficacy of photothermal chemotherapy (HDP-GNR-DOX + NIR) and additive efficacy of single PTT((HDP-GNR + NIR) and chemotherapy (HDP-GNR-DOX)

    图  10  不同剂型对MCF-7的(a)毒性和(b)凋亡的影响

    Figure  10.  (a) Fluorescence images and (b) apoptosis of MCF-7 treated with different formulations

  • [1] MA W, CHEN Q L, XU W G, et al. Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer [J]. Nano Research,2021,14(3):846-857. doi: 10.1007/s12274-020-3124-y
    [2] TANG H L, XU X J, CHEN Y X, et al. Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy [J]. Advanced Materials,2021,33(12):2006003. doi: 10.1002/adma.202006003
    [3] MULENS-ARIAS V, NICOLAS-BOLUDA A, PINTO A, et al. Tumor-selective immune-active mild hyperthermia associated with chemotherapy in colon peritoneal metastasis by photoactivation of fluorouracil-gold nanoparticle complexes [J]. ACS Nano,2021,15(2):3330-3348. doi: 10.1021/acsnano.0c10276
    [4] LIU X L, DONG X, YANG S C, et al. Biomimetic liposomal nanoplatinum for targeted cancer chemophototherapy [J]. Advanced Science,2021,8(8):2003679. doi: 10.1002/advs.202003679
    [5] HE C, ZHANG X, CHEN C, et al. A solid lipid coated calcium peroxide nanocarrier enables combined cancer chemo/chemodynamic therapy with O2/H2O2 self-sufficiency [J]. Acta Biomaterialia,2021,122:354-364. doi: 10.1016/j.actbio.2020.12.036
    [6] HOU G, QIAN J, XU W, et al. Multifunctional PEG-b-polypeptide-decorated gold nanorod for targeted combined chemo-photothermal therapy of breast cancer [J]. Colloids Surfaces B: Biointerfaces,2019,181:602-611. doi: 10.1016/j.colsurfb.2019.05.025
    [7] CHENG Y J, HU J J, QIN S Y, et al. Recent advances in functional mesoporous silica-based nanoplatforms for combinational photo-chemotherapy of cancer [J]. Biomaterials,2020,232:119738. doi: 10.1016/j.biomaterials.2019.119738
    [8] LI J, HUANG X, HUANG R, et al. Erythrocyte membrane camouflaged graphene oxide for tumor-targeted photothermal-chemotherapy [J]. Carbon,2019,146:660-670. doi: 10.1016/j.carbon.2019.02.056
    [9] ZHANG H, LIU P, WANG H, et al. Label-free fluorescent sensor for one-step lysozyme detection via positively charged gold nanorods [J]. Analytical and Bioanalytical Chemistry,2021,413(6):1541-1547. doi: 10.1007/s00216-020-02814-2
    [10] POUDEL B K, GUPTA B, RAMASAMY T, et al. PEGylated thermosensitive lipid-coated hollow gold nanoshells for effective combinational chemo-photothermal therapy of pancreatic cancer [J]. Colloids Surfaces B: Biointerfaces,2017,160:73-83. doi: 10.1016/j.colsurfb.2017.09.010
    [11] DUAN Q, YANG M, ZHANG B, et al. Gold nanoclusters modified mesoporous silica coated gold nanorods: Enhanced photothermal properties and fluorescence imaging [J]. Journal of Photochemistry and Photobiology B: Biology,2021,215:112111. doi: 10.1016/j.jphotobiol.2020.112111
    [12] JAYAWARDENA H S N, LIYANAGE S H, RATHNAYAKE K, et al. Analytical methods for characterization of nanomaterial surfaces [J]. Analytical Chemistry,2021,93(4):1889-1911. doi: 10.1021/acs.analchem.0c05208
    [13] PATEL U, RATHNAYAKE K, JANI H, et al. Near-infrared responsive targeted drug delivery system that offer chemo-photothermal therapy against bacterial infection [J]. Nano Select,2021,2(9):1750-1769.
    [14] QI Z, SHI J, ZHU B, et al. Gold nanorods/graphene oxide nanosheets immobilized by polydopamine for efficient remotely triggered drug delivery [J]. Journal of Materials Science,2020,55(29):14530-14543. doi: 10.1007/s10853-020-05050-2
    [15] PERALTA D V, HEIDARI Z, DASH S, et al. Hybrid paclitaxel and gold nanorod-loaded human serum albumin nanoparticles for simultaneous chemotherapeutic and photothermal therapy on 4T1 breast cancer cells [J]. ACS Applied Materials & Interfaces,2015,7(13):7101-7111.
    [16] WANG D, XU Z, YU H, et al. Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods [J]. Biomaterials,2014,35(29):8374-8384. doi: 10.1016/j.biomaterials.2014.05.094
    [17] XU M, QIAN J, SUO A, et al. Stimuli-responsive terpolymer mPEG-b-PDMAPMA-b-PAH mediated co-delivery of adriamycin and siRNA to enhance anticancer efficacy [J]. RSC Advances,2015,5(27):20890-20899. doi: 10.1039/C5RA00348B
    [18] 臧靖, 柯学, 慈天元. 肝素在抗肿瘤药物递送系统中的应用[J]. 功能高分子学报. 2021, 34(3): 215-229.

    ZANG J, KE X, CI T Y. Application of Heparin in anti-tumor drug delivery systems[J]. Journal of Functional Polymers.2021, 34(3): 215-229.
    [19] LIN X, MA W, WU H, et al. Superhydrophobic magnetic poly (DOPAm-co-PFOEA)/Fe3O4/cellulose microspheres for stable liquid marbles [J]. Chemical Communications,2016,52(9):1895-1898. doi: 10.1039/C5CC08842A
    [20] LIU G, QIU Q, AN Z. Development of thermosensitive copolymers of poly(2-methoxyethyl acrylate-co-poly (ethylene glycol) methyl ether acrylate) and their nanogels synthesized by RAFT dispersion polymerization in water [J]. Polymer Chemistry,2012,3(2):504-513. doi: 10.1039/C2PY00533F
    [21] SUO A, QIAN J, XU M, et al. Folate-decorated PEGylated triblock copolymer as a pH/reduction dual-responsive nanovehicle for targeted intracellular co-delivery of doxorubicin and Bcl-2 siRNA [J]. Materials Science and Engineering: C,2017,76:659-672. doi: 10.1016/j.msec.2017.03.124
    [22] GUO Z, GU C, FAN X, et al. Fabrication of anti-human cardiac troponin I immunogold nanorods for sensing acute myocardial damage [J]. Nanoscale Research Letters,2009,4(12):1428-1433. doi: 10.1007/s11671-009-9415-6
    [23] DING J, CHEN J, GAO L, et al. Engineered nanomedicines with enhanced tumor penetration [J]. Nano Today,2019,29:100800. doi: 10.1016/j.nantod.2019:100800
    [24] WANG J, XU W, ZHANG N, et al. X-ray-responsive polypeptide nanogel for concurrent chemoradiotherapy [J]. Journal of Controlled Release,2021,332:1-9. doi: 10.1016/j.jconrel.2021.02.003
    [25] HOU G, QIAN J, XU W, et al. A novel pH-sensitive targeting polysaccharide-gold nanorod conjugate for combined photothermal-chemotherapy of breast cancer [J]. Carbohydrate Polymers,2019,212:334-344. doi: 10.1016/j.carbpol.2019.02.045
    [26] LIU H, PIERRE-PIERRE N, HUO Q. Dynamic light scattering for gold nanorod size characterization and study of nanorod-protein interactions [J]. Gold Bulletin,2012,45(4):187-195. doi: 10.1007/s13404-012-0067-4
    [27] 王月, 沈娜, 卫琦, 等. 高分子键合血管阻断剂与BLZ945纳米药物协同治疗肿瘤 [J]. 功能高分子学报,2020,33(6):522-531.

    WANG Y, SHEN N, WEI Q, et al. Co-bonded vascular disrupting agents and BLZ945 polymeric nanodrug for synergistic cancer therapy [J]. Journal of Functional Polymers,2020,33(6):522-531.
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出版历程
  • 收稿日期:  2021-03-23
  • 网络出版日期:  2021-06-18
  • 刊出日期:  2022-01-13

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