聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统

汤朝晖; 陈学思

doi:10.11777/j.issn1000-3304.2019.19036

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聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统

专论 | 更新时间：2021-01-26

- 聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统
- Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)
- 高分子学报 2019年50卷第6期页码：543-552
- 作者机构：
  
  中国科学院长春应用化学研究所生态环境高分子材料重点实验室　长春 130022
- 作者简介：
  
  [ "陈学思，男，1959年生. 1982年毕业于吉林大学化学系高分子专业，获得学士学位. 1985 ~ 1992年在中国科学院长春应用化学研究所任实习员、助理研究员. 1988年获得中国科学院长春应用化学研究所功能高分子实验室高分子化学专业硕士学位，1997年获得日本早稻田大学应用化学科高分子科学专业博士学位. 1997 ~ 1999年在美国宾夕法尼亚大学医学院从事博士后研究，1999年回到中国科学院长春应用化研究所，任研究员/课题组长，2005年获得国家杰出青年科学基金资助. 主要从事生物可降解高分子的合成及其相关生物医用应用的研究" ]
- 基金信息：
  
  国家自然科学基金(基金号 51833010, 51520105004)资助项目()
- DOI：10.11777/j.issn1000-3304.2019.19036
  中图分类号：
- 纸质出版日期：2019-6，
  
  网络出版日期：2019-5-9，
  
  收稿日期：2019-2-21，
  
  修回日期：2019-4-9，
扫描看全文
汤朝晖, 陈学思. 聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统[J]. 高分子学报, 2019,50(6):543-552.

Zhao-hui Tang, Xue-si Chen. Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)[J]. Acta Polymerica Sinica, 2019,50(6):543-552.
汤朝晖, 陈学思. 聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统[J]. 高分子学报, 2019,50(6):543-552. DOI： 10.11777/j.issn1000-3304.2019.19036.

Zhao-hui Tang, Xue-si Chen. Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)[J]. Acta Polymerica Sinica, 2019,50(6):543-552. DOI： 10.11777/j.issn1000-3304.2019.19036.

摘要

基于聚乙二醇-聚氨基酸载体材料的肿瘤靶向药物输送系统在降低药物毒副作用，在提高治疗指数，增加候选药物成药性方面具有巨大潜力. 本文围绕以聚谷氨酸接枝聚乙二醇为载体的肿瘤靶向药物输送系统，对近年来课题组肿瘤治疗相关基础研究领域的一些进展进行了总结，梳理了高分子载体结构对纳米药物体内行为的影响规律，提出了“边缘与中心”协同治疗和“凝血靶向”的概念，发现了纳米药物的瘤内低渗透性可显著提高血管阻断剂的肿瘤血管靶向性和抑瘤能力，创建了联合使用血管阻断剂纳米药物与乏氧激活前药的高效实体肿瘤治疗新策略.

Abstract

Tumor-targeting drug delivery systems based on poly(ethylene glycol)-poly(amino acid) carriers have great potential in reducing the side effects of anticancer drugs

increasing the therapeutic index

and enhancing the druggability of drug candidates. In this work

recent progresses of our group in the tumor-targeting drug delivery systems with poly(

-glutamic acid)-graft-poly(ethylene glycol) (PLG-

-mPEG) as carrier

are reviewed. The influence of polymer structure on the behavior of nanomedicine

in vivo

is discussed. Several parameters

including PLG molecular weight

mPEG/PLG weight ratio

mPEG chain length and drug loading content

have a significant influence on the plasma pharmacokinetics of the cisplatin-loaded PLG-

-mPEG nanoparticles (CDDP-NPs). The blood circulation time of the nanoparticles is prolonged with increases in PLG molecular weight

mPEG/PLG weight ratio

mPEG chain length and cisplatin loading content. Cooperative treatment concepts

such as " periphery and center” and " coagulation targeting”

are proposed. By coadministering a vascular disrupting agent (VDA) CA4P and CDDP-NPs

the CDDP-NPs mainly locates at the tumor periphery and leaves most of cancer cells at tumor center viable

the CA4P can make up defect of CDDP-NPs and efficiently kill cancer cells in tumor central regions. The " coagulation targeting” delivery platform comprises a coagulation-inducing agent and coagulation-targeted polymeric nanoparticles. As a typical VDA

DMXAA can create a unique artificial coagulation environment with additional binding sites in a solid tumor by locally activating a coagulation cascade. Coagulation-targeted cisplatin-loaded nanoparticles can selectively accumulate in the solid tumor by homing to the VDA-induced artificial coagulation environment through transglutamination. We discover that the low permeability of nanomedicine in solid tumors can significantly improve the targeting to tumor blood vessels and tumor inhibition ability of VDAs. This provides a new idea for enhancing the therapeutic effect of VDAs in tumor treatment. A powerful combinational strategy is created with nanomedicine of VDAs plus hypoxia-activated prodrugs (HAPs) for the treatment of solid tumors. The nanomedicine of VDAs can selectively enhance tumor hypoxia and boost a typical HAP tirapazamine therapy against metastatic 4T1 breast tumors.

关键词

聚谷氨酸肿瘤靶向纳米药物顺铂血管阻断剂

Keywords

Poly(L-glutamic acid)Tumor targetingNanomedicineCisplatinVascular disrupting agent

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