Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors

Jiaqi Yan; Chang Liu; Qiwei Wu; Junnian Zhou; Xiaoyu Xu; Lirong Zhang; Dongqing Wang; Fan Yang; Hongbo Zhang

doi:10.1021/acs.analchem.0c02599

Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors

Jiaqi Yan, Chang Liu, Qiwei Wu, Junnian Zhou, Xiaoyu Xu, Lirong Zhang, Dongqing Wang, Fan Yang, Hongbo Zhang

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Abstract

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.

Original language	English
Pages (from-to)	11453-11461
Number of pages	9
Journal	Analytical Chemistry
Volume	92
Issue number	16
DOIs	https://doi.org/10.1021/acs.analchem.0c02599
Publication status	Published - 18 Aug 2020
MoE publication type	A1 Journal article-refereed

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10.1021/acs.analchem.0c02599Licence: CC BY

Yan et al., 2020 ACAccepted author manuscript, 2.77 MBLicence: CC BY-NC-ND

https://urn.fi/URN:NBN:fi-fe202201147832

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Takeda, A., Marjamäki, A., Roivainen, A., Hakanen, A., Hänninen, A., Sahlgren, C., Julkunen, I., Ivaska, J., Eriksson, J., Jorma, T., Rinne, J., Knuuti, J., Westermarck, J., Jyrki, H., Gidwani, K., Elima, K., Aires, L., Elo, L. L., Hollmen, M., Johnson, M., Salmi, M., Oresic, M., Poutanen, M., Kortelainen, M., Pentikäinen, O., Raitakari, O., Jaakkola, P., Salminen, P., Taimen, P., Vallittu, P., Rantakari, P., Mattila, P., Nuutila, P., He, Q., Lahesmaa, R., De Figueiredo, R., Jalkanen, S., Lönnberg, T., Soukka, T., Salminen, T. A., Veromaa, T., Lamminmäki, U., Launis, V., Peltola, V., Xiang-Guo, L., Coffey, E., Meinander, A., Toivola, D. & Zhang, H.
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Zhang, H.
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Project: Academy of Finland/Other Research Councils

Cite this

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title = "Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors",

abstract = "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.",

author = "Jiaqi Yan and Chang Liu and Qiwei Wu and Junnian Zhou and Xiaoyu Xu and Lirong Zhang and Dongqing Wang and Fan Yang and Hongbo Zhang",

year = "2020",

month = aug,

day = "18",

doi = "10.1021/acs.analchem.0c02599",

language = "English",

volume = "92",

pages = "11453--11461",

journal = "Analytical Chemistry",

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T1 - Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors

AU - Yan, Jiaqi

AU - Liu, Chang

AU - Wu, Qiwei

AU - Zhou, Junnian

AU - Xu, Xiaoyu

AU - Zhang, Lirong

AU - Wang, Dongqing

AU - Yang, Fan

AU - Zhang, Hongbo

PY - 2020/8/18

Y1 - 2020/8/18

N2 - 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.

AB - 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.

U2 - 10.1021/acs.analchem.0c02599

DO - 10.1021/acs.analchem.0c02599

M3 - Article

VL - 92

SP - 11453

EP - 11461

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 16

ER -

Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors

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InFLAMES: Innovation Ecosystem based on the Immune System

Targeted delivery of CRISPR/Cas9 for advanced liver cancer therapy through c-Myc knockout

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