基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗

刘畅; 陈宇欣; 王江帆; 罗萱; 黄宇迪; 徐瑾蕾; 鄢国平; 陈思; 张先正

doi:10.11777/j.issn1000-3304.2017.17335

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基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗

研究论文 | 更新时间：2021-01-26

- 基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗
- A Multi-functional Drug Delivery System Based on Dendritic Peptide for Tumor Nuclear Accurate Targeting Therapy
- 高分子学报 2018年0卷第6期页码：682-691
- 作者机构：
  
  1.武汉工程大学材料科学与工程学院　武汉 430205
  2.生物医用高分子材料教育部重点实验室武汉大学化学与分子科学学院　武汉 430072
- 作者简介：
  
  E-mail: chensi1989@whu.edu.cn Si Chen, E-mail: chensi1989@whu.edu.cn
  E-mail: xz-zhang@whu.edu.cn Xian-zheng Zhang, E-mail: xz-zhang@whu.edu.cn
- 基金信息：
  
  湖北省教育厅科学技术研究项目(项目号 Q20171509，Q20171504)、武汉工程大学科学基金(基金号 K201701)和武汉工程大学校长基金(基金号 2017032)资助项目()
- DOI：10.11777/j.issn1000-3304.2017.17335
  中图分类号：
- 纸质出版日期：2018-6，
  
  收稿日期：2017-12-25，
  
  修回日期：2018-2-6，
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刘畅, 陈宇欣, 王江帆, 罗萱, 黄宇迪, 徐瑾蕾, 鄢国平, 陈思, 张先正. 基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗[J]. 高分子学报, 2018,0(6):682-691.

Chang Liu, Yu-xin Chen, Jiang-fan Wang, Xuan Luo, Yu-di Huang, Jin-lei Xu, Guo-ping Yan, Si Chen, Xian-zheng Zhang. A Multi-functional Drug Delivery System Based on Dendritic Peptide for Tumor Nuclear Accurate Targeting Therapy[J]. Acta Polymerica Sinica, 2018,0(6):682-691.
刘畅, 陈宇欣, 王江帆, 罗萱, 黄宇迪, 徐瑾蕾, 鄢国平, 陈思, 张先正. 基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗[J]. 高分子学报, 2018,0(6):682-691. DOI： 10.11777/j.issn1000-3304.2017.17335.

Chang Liu, Yu-xin Chen, Jiang-fan Wang, Xuan Luo, Yu-di Huang, Jin-lei Xu, Guo-ping Yan, Si Chen, Xian-zheng Zhang. A Multi-functional Drug Delivery System Based on Dendritic Peptide for Tumor Nuclear Accurate Targeting Therapy[J]. Acta Polymerica Sinica, 2018,0(6):682-691. DOI： 10.11777/j.issn1000-3304.2017.17335.

摘要

为了改善在肿瘤治疗过程中，药物载体靶向性差和药物靶点定位效率低等不足，设计了一种能精准靶向肿瘤细胞核，将药物高效递送至作用靶点的多功能纳米载药体系. 利用具有细胞核定位能力的两亲性枝化多肽包载化疗药物阿霉素(DOX)形成载药纳米胶束DD，并通过静电作用将具有肿瘤靶向功能的透明质酸(HA)包覆在DD表面，得到具有靶向肿瘤细胞核能力的纳米药物HDD. HA的存在赋予了HDD对肿瘤的靶向功能和电荷屏蔽能力，可增加体系的稳定性，延长其血液循环时间，降低正常组织和细胞对HDD的非特异性摄取，实现其在肿瘤部位的特异性富集和肿瘤细胞的高效摄取. 进入肿瘤细胞后，HA层的降解有利于纳米胶束DD在多肽的核定位作用下精准、快速地将DOX递送至细胞核，最终实现高效的肿瘤抑制效果.

Abstract

Though chemotherapeutics has been one of the most widely used treatments for tumor therapy

it is still heavily limited due to its poor pharmacokinetics

undesirable intracellular uptake and inevitable side effects. In order to overcome these barriers

various functional groups have been introduced in drug delivery system to enhance the therapeutic efficiency of chemotherapy. In this study

a novel drug delivery system for tumor nuclear accurate targeting was designed in order to achieve precise tumor nuclear treatment. The chemotherapeutic drug (doxorubicin

DOX) was encapsulated in amphiphilic dendritic peptide with nuclear localization function to form a regular nanoparticle DD. After that

electronegative hyaluronic acid (HA) with ability of tumor targeting was coated on the surface of nanoparticle DD

via

electrostatic interaction to form tumor nuclear targeting drug delivery system HDD. The presence of HA endowed HDD with the tumor targeting ability and charge shielding effect

which could increase the stability of nanodrug

promote the specific internalization by tumor cells and reduce the non-specific uptake by normal tissue/cells. Furthermore

it was found that the drug delivery system HDD could realize the facile internalization by tumor cells

via

CD44 receptor-mediated recognition. After the degradation of HA shell by hyaluronidase (HAase) in endosome

the nuclear targeted nanodrug DD was exposed

and DOX was carried to the region of nuclear accurately by inheriting the ability from nuclear-targeted peptide. The precise targeting of drug to nuclei could be beneficial to the improvement of drug utilization as well as the suppression of tumor cells. The characteristics of this tumor nuclear accurate targeting drug delivery system

including particle sizes

zeta potential

drug loading capacity

drug release behavior

cellular uptake and antitumor efficacy

were evaluated. All of the studies confirmed that the precise tumor nuclear targeting drug delivery system HDD displayed prominent antitumor efficacy with insignificant adverse effects to normal cells

in vitro

which indicated that the precise tumor nuclear targeting delivery system supplies a useful strategy for tumor therapy.

关键词

枝化多肽纳米药物肿瘤靶向核定位精准治疗

Keywords

Dendritic peptideNanodrugTumor-targetingNuclear localizationPrecise treatment

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