同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体

郑西西; 林辉; 王利群

doi:10.11777/j.issn1000-3304.2017.17019

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同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体

研究论文 | 更新时间：2021-01-26

- 同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体
- Fabrication of MMP-2 Rresponsive Nanoparticles by Coaxial Electrospray-template Removal
- 高分子学报 2017年第11期页码：1789-1795
- 作者机构：
  
  1.浙江大学高分子科学与工程学系
  2.高分子合成与功能构造教育部重点实验室杭州 310027
  3.浙江大学医学院附属邵逸夫医院杭州 310016
- 作者简介：
  
  王利群, E-mail: lqwang@zju.edu.cn Li-qun Wang, E-mail: lqwang@zju.edu.cn
- 基金信息：
  
  国家自然科学基金(21474086)
- DOI：10.11777/j.issn1000-3304.2017.17019
  中图分类号：
- 纸质出版日期：2017-11-20，
  
  收稿日期：2017-1-18，
  
  修回日期：2017-2-15，
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郑西西, 林辉, 王利群. 同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体[J]. 高分子学报, 2017,(11):1789-1795.

Xi-xi Zheng, Hui Lin, Li-qun Wang. Fabrication of MMP-2 Rresponsive Nanoparticles by Coaxial Electrospray-template Removal[J]. Acta Polymerica Sinica, 2017,(11):1789-1795.
郑西西, 林辉, 王利群. 同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体[J]. 高分子学报, 2017,(11):1789-1795. DOI： 10.11777/j.issn1000-3304.2017.17019.

Xi-xi Zheng, Hui Lin, Li-qun Wang. Fabrication of MMP-2 Rresponsive Nanoparticles by Coaxial Electrospray-template Removal[J]. Acta Polymerica Sinica, 2017,(11):1789-1795. DOI： 10.11777/j.issn1000-3304.2017.17019.

摘要

通过化学键偶联的形式在聚乳酸（PLA）分子链中引入了可被金属基质蛋白酶（MMP-2）特异性降解的多肽peptide（GPLGIAGQ）单元，得到具有金属基质蛋白酶响应性的聚合物PLA-

-peptide-

-PLA.通过同轴电喷方法制备得到以PLA-

-peptide-

-PLA和抗肿瘤药物DOX的混合物作为内核，亲水性聚乙二醇（PEG）作为外壳的，具有核-壳结构的载药微球.其中水溶性的PEG壳层可在水环境中迅速脱除，将载药微球的尺寸从微米级减小到纳米尺度，可以达到药物载体系统在输运的循环过程中的尺寸递减.制备的纳米载体可在金属基质蛋白酶存在的环境中，响应性释放所包载的抗肿瘤药物，实现药物的控制释放.

Abstract

Peptide (Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln)

which can be specifically degraded by matrix metalloproteinases 2 (MMP-2)

was conjugated into polylactic acid (PLA)

constructing therefore a new type of MMP-responsive drug delivery system (DDS). Microparticles with core-shell structure were fabricated using coaxial electrospray. PEG was used as the shell and PLA-

-peptide-

-PLA as the core material. The water-soluble PEG shell was quickly removed from aqueous environment and the size of the microspheres was reduced from micron to nanometer scale. Eventually

MMP-2 responsive nanoparticles with a diameter of about 100 nm were obtained through coaxial electrospray-template removal method. MMP-2 response of the nanoparticles was investigated by the change of particle size and morphology with DLS and TEM. After coculturing with MMP-2 protease

the spherical skeleton of the nanoparticles was partly degraded. Meanwhile

part of the degraded particles got aggregated. This is because MMP-2 protease specifically cleave the peptide

resulting in the partly disassembly of the nanoparticles and random reassembling of PLA. Doxorubicin (DOX) was used as a model chemotherapeutic drug and loaded in the core of the nanoparticles. The drug loading content and entrapment efficiency of DOX were 0.326% and 75.3%

respectively. The

in vitro

release profile of DOX from the electrosprayed particles was studied. It was found that the encapsulated DOX was released from the nanoparticles

and the release was controlled by the stimulus of overexpressed MMP-2 protease

and the process lasted more than 20 days. The results show that coaxial electrospray-template removal method did not affect the matrix metalloproteinases response of the peptide

and thus the nanoparticles prepared have good MMP-2 responsiveness. Meanwhile

the size of the particles can be modulated by the coaxial electrospray-template removal method

and the nano-sized particles can be simply and effectively achieved. The study suggests that the coaxial electrospray-template removal method is a promising route to the preparation of stimuli-responsive drug delivery system.

关键词

电喷金属基质蛋白酶核壳结构抗肿瘤

Keywords

ElectrosprayMatrix metalloproteinases (MMPs)Core-shell structureAntitumor

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