TY - JOUR
T1 - Biotin-decorated celastrol-loaded ZIF-8 nanoparticles induce ferroptosis for colorectal cancer therapy
AU - Chen, Jie
AU - Liu, Yan
AU - You, Yanting
AU - Zhou, Ruisi
AU - Li, Yanchun
AU - Zhou, Xinghong
AU - Chen, Xiaohu
AU - Yang, Ying
AU - Chen, Jinxiang
AU - Kwan, Hiu Yee
AU - Zhao, Xiaoshan
AU - Wu, Yuyao
N1 - This research received support from funding provided by the National Key R&D Program of China (2020YFC2003100, 2020YFC2003101), the Natural Science Foundation of Guangdong Province (2021A1515110990), China Postdoctoral Science Foundation (2022M711537), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202001).
Publisher Copyright:
© 2024 The Authors. Published by Elsevier Ltd.
PY - 2024/3
Y1 - 2024/3
N2 - Celastrol (CEL) has garnered significant interest for its anti-tumour properties and potential for colorectal cancer (CRC) treatment. However, its clinical use is constrained by its limited bioavailability and potential toxicity. Herein, a biotin-decorated CEL nano-drug delivery system using a zeolitic imidazolate framework (ZIF-8) as a carrier was synthesized, named CEL@ZIF-8@BIO. It exhibits excellent water solubility, efficient loading of CEL, and a high release rate in acidic environments. In vitro experiments demonstrated that CEL@ZIF-8@BIO inhibited proliferation, induced cell cycle arrest in G0/G1 phase, increased ROS production and reduced mitochondrial membrane potential in CRC cells. RNA-Seq analysis indicated that the anticancer mechanism of CEL@ZIF-8@BIO may be linked to ferroptosis as indicated by a significant increase in Fe2+ levels, oxidative stress, lipid peroxidation, and mitochondrial dysfunction in CRC cells. Furthermore, these effects could be reversed by ferroptosis inhibitor. In vivo research revealed that CEL@ZIF-8@BIO significantly inhibited the growth of CRC tumours and reduced the toxicity associated with CEL treatment. Taken together, the CEL@ZIF-8@BIO nano-drug delivery system shows great promise for CRC therapy due to its improved efficacy and reduced toxicity.
AB - Celastrol (CEL) has garnered significant interest for its anti-tumour properties and potential for colorectal cancer (CRC) treatment. However, its clinical use is constrained by its limited bioavailability and potential toxicity. Herein, a biotin-decorated CEL nano-drug delivery system using a zeolitic imidazolate framework (ZIF-8) as a carrier was synthesized, named CEL@ZIF-8@BIO. It exhibits excellent water solubility, efficient loading of CEL, and a high release rate in acidic environments. In vitro experiments demonstrated that CEL@ZIF-8@BIO inhibited proliferation, induced cell cycle arrest in G0/G1 phase, increased ROS production and reduced mitochondrial membrane potential in CRC cells. RNA-Seq analysis indicated that the anticancer mechanism of CEL@ZIF-8@BIO may be linked to ferroptosis as indicated by a significant increase in Fe2+ levels, oxidative stress, lipid peroxidation, and mitochondrial dysfunction in CRC cells. Furthermore, these effects could be reversed by ferroptosis inhibitor. In vivo research revealed that CEL@ZIF-8@BIO significantly inhibited the growth of CRC tumours and reduced the toxicity associated with CEL treatment. Taken together, the CEL@ZIF-8@BIO nano-drug delivery system shows great promise for CRC therapy due to its improved efficacy and reduced toxicity.
KW - Celastrol
KW - Colorectal cancer
KW - Ferroptosis
KW - Zeolitic imidazolate framework-8
KW - Nano-drug
UR - http://www.scopus.com/inward/record.url?scp=85186513769&partnerID=8YFLogxK
U2 - 10.1016/j.matdes.2024.112814
DO - 10.1016/j.matdes.2024.112814
M3 - Journal article
AN - SCOPUS:85186513769
SN - 0264-1275
VL - 239
JO - Materials and Design
JF - Materials and Design
M1 - 112814
ER -
