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癌症基因靶向治疗用高细胞摄取可注射纳米马达-水凝胶递送系统

任姣雨 王虹

任姣雨, 王虹. 癌症基因靶向治疗用高细胞摄取可注射纳米马达-水凝胶递送系统[J]. 复合材料学报, 2022, 40(0): 1-8
引用本文: 任姣雨, 王虹. 癌症基因靶向治疗用高细胞摄取可注射纳米马达-水凝胶递送系统[J]. 复合材料学报, 2022, 40(0): 1-8
Jiaoyu REN, Hong WANG. Injectable nanomotors-hydrogel system with high cellular uptake for targeted cancer gene therapy[J]. Acta Materiae Compositae Sinica.
Citation: Jiaoyu REN, Hong WANG. Injectable nanomotors-hydrogel system with high cellular uptake for targeted cancer gene therapy[J]. Acta Materiae Compositae Sinica.

癌症基因靶向治疗用高细胞摄取可注射纳米马达-水凝胶递送系统

基金项目: 国家自然科学基金(21905303);江苏省自然科学基金(BK20180635);中央高校基本科研业务费专项资金(2021 QN1041)
详细信息
    通讯作者:

    王虹,博士研究生,教授,博士生导师,研究方向为微纳马达 E-mail: hongwang@cumt.edu.cn

  • 中图分类号: TB333

Injectable nanomotors-hydrogel system with high cellular uptake for targeted cancer gene therapy

Funds: National Natural Science Foundation of China (21905303);Natural Science Foundation of Jiangsu Province (BK20180635); Fundamental Research Funds for the Central Universities (2021 QN1041)
  • 摘要: 小干扰 RNA (siRNA) 由于其降低基因表达的能力,通常在基因治疗中充当重要的治疗剂。然而,siRNA的低细胞摄取限制了其在癌症治疗中的功效。本文报告了一种生物相容的纳米马达-水凝胶递送系统,使siRNA可在癌症靶向治疗中获得高细胞摄取率。首先通过层层自组装技术,以铂纳米粒子为核,使用聚乙烯亚胺(PEI)和聚苯乙烯磺酸钠(PSS)制备载有siRNA的纳米马达(NM)。为了瘤内给药和缓释,将纳米马达装载在席夫碱水凝胶中,构建NM-hydrogel系统。肿瘤微环境具有弱酸性和高过氧化氢含量的特点。水凝胶响应弱酸性微环境释放纳米马达,释放的纳米马达可以通过过氧化氢的催化分解实现自驱动,其运动速度在1% H2O2下为1.78 µm/s(每秒约22.25个体长)。纳米马达的自驱动性能和由纳米马达上修饰的叶酸(FA)介导的特定内吞作用使NM-hydrogel系统具有63.8%的高细胞摄取率。同时,自驱动性能和PEI引起的质子海绵效应促进了纳米马达在肿瘤细胞中的深度渗透和长时间滞留,从而促进了NM-hydrogel系统的抗癌作用。结果表明,该体系在72 h时的抗癌活性为74.8%。同时,NM-hydrogel系统具有良好的生物相容性和生物降解性,为其未来在体内基因治疗中的应用奠定了基础。

     

  • 图  1  (a)负载小干扰RNA的纳米马达(siRNA@NM)合成示意图;siRNA@NM的SEM图像(b)、TEM图像(c)和紫外-可见光谱(d)

    Figure  1.  (a) Schematic fabrication process of nanomotors loaded with Small interfering RNA (siRNA) (siRNA@NM); SEM image (c), TEM image (d) and UV-visible transmission spectra (b) of siRNA@NM.

    图  2  (a) siRNA@NM在不同H2O2溶液中的运动轨迹;(b) siRNA@NM在不同H2O2溶液中的速度和有效扩散系数;(c) siRNA@NM在不同H2O2溶液中的MSD-△t曲线

    Figure  2.  (a) Motion trajectories of siRNA@NM in different H2O2 solution; (b) The velocity and the effective diffusion coefficients of the siRNA@NM in different H2O2 solution; (c) The MSD-△t plot of siRNA@NM in different H2O2 solution.

    图  3  (a) 席夫碱水凝胶的SEM图像;(b) 双醛淀粉(DS)、壳聚糖(CS)和席夫碱水凝胶的红外光谱;(c) NM-hydrogel系统的SEM图像;(d) siRNA@NMs在PBS溶液(pH6.5/ pH7.4)中的释放曲线

    Figure  3.  (a) SEM image of Schiff-base hydrogel; (b) FTIR spectra of dialdehyde starch (DS), chitosan (CS) and Schiff-base hydrogel; (c) the SEM image of NM-hydrogel system; (d) the time-dependent release of siRNA@NMs from the NM-hydrogel system in PBS solution (pH 6.5/ pH 7.4).

    图  4  (a) NM-hydrogel系统的抗癌活性;(b) NM-hydrogel系统处理后,4T1细胞的活死染色

    Figure  4.  (a) The anticancer activity of NM-hydrogel system; (b) live-dead staining of 4T1 cells after injected with NM-hydrogel system

    图  5  NM-hydrogel系统的细胞毒性(a)和生物降解性(b)

    Figure  5.  The cell cytotoxicity (a) and biodegradation property (b) of NM-hydrogel system

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出版历程
  • 收稿日期:  2022-03-21
  • 录用日期:  2022-05-13
  • 修回日期:  2022-04-28
  • 网络出版日期:  2022-06-01

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