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

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

西安交通大学，金属材料强度国家重点实验室，西安 710049

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
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- 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

Preparation of Stimulus-Responsive Copolymer-Decorated Gold Nanorods and Their Anti-tumor Effects

State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an 710049, China

摘要

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。
- 嵌段共聚物 /
- 金纳米棒 /
- 联合治疗 /
- 光热治疗
Abstract: A triblock copolymer with mussel-inspired adhesive ability, poly(acryl hydrazide)-b-poly(N-(3, 4-dihydroxyphenylethyl) acrylamide)-b-poly(monomethoxypolyethylene glycol acrylate) (HDP), was designed and synthesized via reversible addition fragmentation chain transfer polymerization process from three monomers, including 1-tert-butoxycarbonyl-2-acrylhydrazide(Boc-AH), N-(3, 4-dihydroxyphenylethyl) acrylamide and poly(ethylene glycol) methyl ether methacrylate (mPEGA). The copolymer was used for decorating gold nanorod (GNR) to obtain GNR-based nanocarrier. Chemotherapeutic drug doxorubicin (DOX) was conjugated onto the nanocarrier by an acid-labile hydrazone linkage, resulting in HDP-GNR-DOX nanodrug. The physicochemical properties of the nanocarrier, such as structure, stability, photothermal performance, and pH responsive drug release, were characterized. Moreover, the in vitro anti-tumor effect of the nanodrug towards breast cancer cells (MCF-7) was evaluated. Results showed that the DOX content of the nanodrug was as high as 8.1% and the nanodrug exhibited excellent photothermal conversion ability, favorable stability and pH-responsive drug release behavior. Importantly, cell experimental results demonstrated that the nanodrug could be effectively internalized by MCF-7 cells. In the case of near infrared irradiation, the nanodrug showed high apoptosis-inducing ability on MCF-7 cells, achieving highly efficient photothermal-chemotherapy of breast cancer.
- block copolymer /
- gold nanorod /
- combination therapy /
- photothermal therapy

HTML全文

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

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图 2 样品的¹H-NMR谱图

Figure 2. ¹H-NMR spectra of samples

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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

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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）

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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

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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

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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

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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

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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

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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

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