A1 Refereed original research article in a scientific journal
Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors
Authors: Yan Jiaqi, Liu Chang, Wu Qiwei, Zhou Junnian, Xu Xiaoyu, Zhang Lirong, Wang Dongqing, Yang Fan, Zhang Hongbo
Publisher: AMER CHEMICAL SOC
Publication year: 2020
Journal: Analytical Chemistry
Journal name in source: ANALYTICAL CHEMISTRY
Journal acronym: ANAL CHEM
Volume: 92
Issue: 16
First page : 11453
Last page: 11461
Number of pages: 9
ISSN: 0003-2700
eISSN: 1520-6882
DOI: https://doi.org/10.1021/acs.analchem.0c02599
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/52242178
The zeolitic imidazolate framework (ZIF-8), composed of zinc ion and dimethylimidazole, is widely used in drug delivery because of the easy fabrication process and the good biosafety. However, ZIF-8 suffers from low affinity to nonelectric-rich drugs and does not have surface functional groups. Here, to deliver doxorubicin (DOX) with ZIF-8 to specific target sites, DOX was first modified with a pH-sensitive linker containing two carboxyl groups to form the inactive prodrug CAD and subsequently seeded inside ZIF-8 by a 5 min mineralization process. CAD has high affinity to ZIF-8 because of the carboxyl groups and can anchor to the ZIF-8 surface to enable the surface modification with folic acid for tumor targeting. Moreover, the DOX release is precisely controlled by three steps of acidic pH response, with the dissociation of the FA layer, the breakdown of the ZIF-8 structure, and the cleavage of the pH-sensitive linker in prodrug. This novel "prodrug-ZIF-8" strategy has opened a new horizon in drug delivery.
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