Citation: 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, ;2018, 0(8): 1089-1096. doi: 10.11777/j.issn1000-3304.2018.18035 shu

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

Ministry of Education Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027

Corresponding author: Jian Ji, jijian@zju.edu.cn
Received Date: 1 February 2018
Revised Date: 12 February 2018
Available Online: 13 April 2018

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 β-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 β-CD-hydrazone-DOX was confirmed by 2D ¹H 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.
- Host-guest interactions,
- Supramolecule,
- Drug delivery,
- Imaging
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