ISSN 1000-3304CN 11-1857/O6

酸敏感高分子纳米药物载体在肿瘤治疗中的应用研究

高晶 王伟奇 于海军

引用本文: 高晶, 王伟奇, 于海军. 酸敏感高分子纳米药物载体在肿瘤治疗中的应用研究[J]. 高分子学报, 2019, (11): 1156-1166. doi: 10.11777/j.issn1000-3304.2019.19133 shu
Citation:  Jing Gao, Wei-qi Wang and Hai-jun Yu. Acid-activatable Polymeric Drug Delivery Systems for Cancer Therapy[J]. Acta Polymerica Sinica, 2019, (11): 1156-1166. doi: 10.11777/j.issn1000-3304.2019.19133 shu

酸敏感高分子纳米药物载体在肿瘤治疗中的应用研究

    作者简介: 于海军,男,1978年生. 中科院上海药物研究所研究员,博士生导师,课题组长. 2001年大学本科毕业于内蒙古大学,2006年获得中国科学院长春应用化学研究所高分子化学博士学位,随后在德国慕尼黑大学、美国西南医学中心和日本东北大学进行博士后研究,2012年回国加入中国科学院上海药物研究所. 曾获国家基金委优秀青年科学基金(2016年)、科技部中青年科技创新领军人才(2017年)、中国科学院青年创新人才促进会优秀会员(2018年)等荣誉和人才项目资助. 曾获中国药学会科学技术奖一等奖和中国药学会-赛诺菲青年生物药物奖等奖励. 主要从事新型药物递送系统和生物医用功能材料等领域的基础和应用研究;
    通讯作者: 于海军, E-mail: hjyu@simm.ac.cn
摘要: 纳米递药系统有望实现药物靶向递送增加其生物利用度、降低其毒副作用,在肿瘤治疗方面受到了广泛关注. 但是,抗肿瘤药物的体内递送是一个多步骤的复杂过程,如何有效克服肿瘤组织(肿瘤部位的特异性富集滞留、深部渗透、高效细胞摄取)及细胞内(胞内可控药物释放)的多重物理屏障是抗肿瘤纳米递药系统面临的重大挑战. 利用肿瘤组织及细胞内的微酸环境,在药物载体材料中引入酸响应化学键或功能基团,构建酸响应性纳米递药系统是实现肿瘤特异性药物递送、提高药物递送效率的有效途径. 本文系统回顾了本课题组近年来在运用酸敏感高分子载体材料设计构建智能纳米递药系统,克服药物递送的关键物理屏障,改善肿瘤治疗效果方面的研究进展,并对其转化前景进行了展望.

English

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  • Figure 1.  Schematic of pH-sensitive nanoparticle-based drug delivery system in the tumour microenvironment: (a) The pH-sensitive nanoparticles stay ‘OFF’ at pH 7.4 during blood circulation (After reaching tumours, these nanoparticles are turned ‘ON’ by acidic extracellular pHe (6.5 − 6.8), or endocytic organelles pHi (5.0 − 6.0)); (b) The process of drug release in tumor cells; (c) Chemical structures of the pH-responsive components or functional groups

    Figure 2.  (a) Schematic illustration of the ASPN; (b, c) Diameter of ASPN at pH = 7.4 and pH = 6.5, respectively; (c, d) TEM images of ASPN at pH = 7.4 and pH = 6.5, respectively; Cellular uptake measured by CLSM (f) images and (g) the profile of fluorescence intensity (Reproduced with permission from Ref.[26]; Copyright (2018) John Wiley and Sons)

    Figure 3.  (a) Schematic illustration of the iPAPD nanoparticles; (b) Acid-activatable iPAPD nanoparticles for tumor therapy; (c) TEM images and diameter of iPAPD nanoparticles at pH = 7.4 and 6.6, respectively; (d) Cellular uptake measured by flow cytometry (**p < 0.05, ***p < 0.01) (Reproduced with permission from Ref.[31]; Copyright (2017) American Chemical Society)

    Figure 4.  (a) Schematic illustration of the acid-switchable micelles; (b) The imaging and tumor therapy of the micelles; (c) The intracellular fluorescence of PDPC micelle in MCF-7/ADR cells with or without Baf-A1 preincubation; (d) The combination of protonation and PDT enhanced endosome escape (Reproduced with permission from Ref.[47]; Copyright (2016) American Chemical Society)

    Figure 5.  (a) Schematic illustration of the acid-switchable micelles for delivery siRNA-PD-L1, and (b) the combination of PDT for enhancing tumor therapeutic efficacy; (c, d) The inhibition of tumor growth and metastatic by combination of PDT and PD-L1 KD (Reproduced with permission from Ref.[59]; Copyright (2016) American Chemical Society)

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  • 通讯作者:  于海军, hjyu@simm.ac.cn
  • 收稿日期:  2019-07-12
  • 修稿日期:  2019-08-09
  • 刊出日期:  2019-11-01
通讯作者: 陈斌, bchen63@163.com
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