Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly

Yin Wang; Hai-bo Wang; Hai-jie Han; Fan Jia; Qiao Jin; Jian Ji

doi:10.11777/j.issn1000-3304.2018.18035

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Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly

Research Article | 更新时间：2021-01-26

- Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly
- Acta Polymerica Sinica Vol. 0, Issue 8, Pages: 1089-1096(2018)
- 作者机构：
  
  教育部高分子合成与功能构造重点实验室浙江大学高分子科学与工程学系　杭州 310027
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2018.18035
  CLC：
- Published：2018-8，
  
  Received：1 February 2018，
  
  Revised：12 February 2018，
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Yin Wang, Hai-bo Wang, Hai-jie Han, Fan Jia, Qiao Jin, Jian Ji. Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly. [J]. Acta Polymerica Sinica 0(8):1089-1096(2018)
DOI：

Yin Wang, Hai-bo Wang, Hai-jie Han, Fan Jia, Qiao Jin, Jian Ji. Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly. [J]. Acta Polymerica Sinica 0(8):1089-1096(2018) DOI： 10.11777/j.issn1000-3304.2018.18035.

摘要

基于

-环糊精和胆固醇之间的主客体识别作用，通过对主客体分子的设计，构筑模块化的组装基元；通过主客体分子组装，将具有靶向功能的乳糖酸、成像功能的异硫氰酸荧光素和治疗作用的阿霉素引入同一超分子聚合物前药胶束中，制备得到多功能的纳米药物传递系统. 研究结果表明，具有不同功能的模块基元可通过超分子主客体组装在水中自组装成一定尺寸的前药胶束，并通过二维

H NOESY谱证明了主客体作用的发生. 该前药胶束具有pH值响应的药物释放行为，在细胞内涵体/溶酶体酸性环境下药物释放速率显著加快. 用荧光显微镜和流式细胞仪对此聚合物前药胶束的细胞内吞行为进行了研究. 在乳糖酸受体介导作用下，聚合物前药胶束能在肿瘤细胞内有效富集，并同时观察到阿霉素和异硫氰酸荧光素的荧光，用以跟踪载体在细胞内的位置. MTT的结果进一步表明，该前药胶束能有效地抑制癌细胞的增殖.

Abstract

Unlike the crude study conducted at the beginning of nanomedicine

researchers have devoted more efforts to developing nanosystems with elaborated structures and multifunctions owing to the fact that the tumor microenvironment is complicated. However

it is still a great challenge to prepare these nanoplatforms for drug delivery. In this study

multifunctional prodrug nanocarriers were fabricated by the modularized host-guest self-assembly between cholesterol and

-cyclodextrin. The targeted ligand lactobionic acid (LBA)

fluorescent probe fluoresceine isothiocyanate (FITC)

and chemtherapeutic drug doxorubicin (DOX) were integrated into the multifunctional supramolecualr drug nanocarriers. The host-guest interaction between Chol-PEG and

-CD-hydrazone-DOX was confirmed by 2D

H NOESY spectrum. The modularized functional building blocks could self-assemble into micelles with a diameter of 20 nm. The supramolecular nanocarriers showed pH-sensitive drug release behavior. The release of DOX can be greatly accelerated in acidic endo/lysosomal pH. The internalization of the supramolecular drug nanocarriers by HepG2 cells was studied by fluorescence microscopy and flow cytometry. The nanocarriers can be well taken up by cancer cells. Due to the targeting ability of LBA

the internalization of the nanocarriers can be greatly inhibited if the cells are pre-treated by free LBA. At the same time

the fluorescence of FITC can be clearly observed intracellularly

which can be used to track the sub-cellular location of the drug nanocarriers. Finally

the cytotoxicity of the drug nanocarriers was investigaed by MTT assay. With the HepG2 cells pre-treated with free LBA

the cytotoxicity of the drug nanocarriers was significantly reduced

most probably owing to the unsatisfactory cell uptake. The concentration-dependent cytotoxicity toward HepG2 cells was also observed. Therefore

the integration of target ligand and imaging ligand have endowed the nanocarriers with targeted theranostic property. More importantly

since the modularized host-guest self-assembly is dynamically tunable

the percentage of functional ligands could be easily optimized to achieve a better outcome. Such multifunctional prodrug nanocarriers fabricated by modularized host-guest self-assembly may have great potential in drug delivery.

关键词

主客体作用超分子药物传递成像

Keywords

Host-guest interactionsSupramoleculeDrug deliveryImaging

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Department of Chemistry & Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University

Chinese Academy of Sciences Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240

Instrumental Analysis Center, Shanghai Jiao Tong University

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