高级检索

  • ISSN 1008-9357
  • CN 31-1633/O6

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

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. 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. 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 Effects[J]. Journal of Functional Polymers. 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 Effects[J]. Journal of Functional Polymers. 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 Effects

  • 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,制备了聚(丙烯酰肼)-b-聚(N-(3,4-二羟基苯乙基)丙烯酰胺)-b-聚(单甲氧基聚乙二醇丙烯酸酯),该共聚物经酚羟基偶联于金纳米棒(GNR)表面,酰肼基团与阿霉素中羰基形成酸敏感的腙键实现药物装载,构建了化疗/光热联合治疗的纳米体系。利用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CLSM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响应性药物释放行为。细胞实验表明,该纳米体系可被乳腺癌细胞(MCF-7)有效摄取,具有光热-化疗协同杀伤肿瘤细胞的效果。

     

  • 图  1  HDP-GNR-DOX纳米药物的制备及其在MCF-7细胞中的作用方式示意图

    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  CTAB-GNR(a)和 HDP-GNR(b)的HRTEM图像

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

    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

    Figure  5.  (a) UV-Vis spectra and Photographs of CTAB-GNR and HDP-GNR-DOX in water and PBS buffer;(b)Release curves of DOX from HDP-GNR-DOX nanodrug

    图  6  (a)样品的光热性能;(b) HDP-GNR-DOX浓度和(c)激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) laser power on photothermal performance;(d)Photothermal stability of HDP-GNR-DOX

    图  7  HDP-GNR-DOX处理MCF-7细胞的(a)TEM图像、(b)流式细胞术结果和(c)细胞内荧光强度

    Figure  7.  (a) TEM images, (b) flow cytometry profiles and (c) fluorescence intensity of MCF-7 cells treated with HDP-GNR-DOX

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

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

    图  9  (a)HDP-GNR的细胞毒性;(b)HDP-GNR-DOX杀伤MCF-7细胞的况;(c)HDP-GNR-DOX协同杀伤肿瘤细胞的效果

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

    图  10  不同剂型对MCF-7细胞的(a)毒性和(b)凋亡的影响

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

  • [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.
    [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.
  • 加载中
图(10)
计量
  • 文章访问数:  86
  • HTML全文浏览量:  44
  • PDF下载量:  27
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-03-23
  • 网络出版日期:  2021-06-18

目录

    /

    返回文章
    返回