TY - JOUR
T1 - Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy
AU - Zhou, Ruisi
AU - You, Yanting
AU - Zha, Zhiqiang
AU - Chen, Jie
AU - Li, Yanchun
AU - Chen, Xiaohu
AU - Chen, Xiaomei
AU - Jiang, Xuefeng
AU - Chen, Jinxiang
AU - Kwan, Hiu Yee
AU - Zhao, Xiaoshan
AU - Huang, Liping
AU - Liu, Yanyan
N1 - Funding Information:
The work was supported by the National Natural Science Foundation of China ( 82074289 , 82104705 , 82104629 ), the Natural Science Foundation of Guangdong Province ( 2021A1515010673 , 2023A1515011078 ), China Postdoctoral Science Foundation ( 2022M711536 , 2022M711537 ), Traditional Chinese Medicine Administration Project of Guangdong Province ( 20221438 , 20221256 ), Medical Scientific Research Foundation of Guangdong Province ( A2021103 ), Science and Technology Program of Yangjiang ( SF2021049 , SF2022001 ), and the Scientific Research Fund of Yangjiang People's Hospital ( 2021003 , G2021004 ).
Publisher Copyright:
© 2023 The Authors.
PY - 2023/11
Y1 - 2023/11
N2 - Ovarian cancer (OC) stands as the second most prominent factor leading to cancer-related fatalities, characterized by a notably low five-year survival rate. The insidious onset of OC combined with its resistance to chemotherapy poses significant challenges in terms of treatment, emphasizing the utmost importance of developing innovative therapeutic agents. Despite its remarkable anti-tumor efficacy, celastrol (CEL) faces challenges regarding its clinical utilization in OC due to its restricted water solubility and notable side effects. In this study, celastrol (CEL) was encapsulated into Zeolitic imidazolate framework-8(ZIF-8) nanoparticle and grafted with biotin-conjugated polyethylene glycol (CEL@ZIF-8@PEG-BIO). Comprehensive comparisons of the physicochemical properties and anticancer activities of CEL and CEL@ZIF-8@PEG-BIO were conducted. Our findings revealed that CEL@ZIF-8@PEG-BIO exhibited favorable characteristics, including hydrodynamic diameters of 234.5 nm, excellent water solubility, high drug loading (31.60% ± 2.85), encapsulation efficiency (60.52% ± 2.79), and minimal side effects. Furthermore, CEL@ZIF-8@PEG-BIO can release chemicals in response to an acidic micro-environment, which is more likely a tumor micro-environment. In vitro, studies showed that CEL@ZIF-8@BIO inhibited cell proliferation, led to mitochondrial membrane potential (MMP) decline, and generated reactive oxygen species in OC cells. Both in vitro and in vivo experiments indicated that CEL@ZIF-8@PEG-BIO enhanced anti-tumor activity against OC via up-regulated apoptosis-promoting biomarkers and rendered cancer cell apoptosis via the P38/JNK MAPK signaling pathway. In conclusion, we have successfully developed a novel drug delivery system (CEL@ZIF-8@PEG-BIO), resulting in significant improvements in both water solubility and anti-tumor efficacy thereby providing valuable insights for future clinical drug development.
AB - Ovarian cancer (OC) stands as the second most prominent factor leading to cancer-related fatalities, characterized by a notably low five-year survival rate. The insidious onset of OC combined with its resistance to chemotherapy poses significant challenges in terms of treatment, emphasizing the utmost importance of developing innovative therapeutic agents. Despite its remarkable anti-tumor efficacy, celastrol (CEL) faces challenges regarding its clinical utilization in OC due to its restricted water solubility and notable side effects. In this study, celastrol (CEL) was encapsulated into Zeolitic imidazolate framework-8(ZIF-8) nanoparticle and grafted with biotin-conjugated polyethylene glycol (CEL@ZIF-8@PEG-BIO). Comprehensive comparisons of the physicochemical properties and anticancer activities of CEL and CEL@ZIF-8@PEG-BIO were conducted. Our findings revealed that CEL@ZIF-8@PEG-BIO exhibited favorable characteristics, including hydrodynamic diameters of 234.5 nm, excellent water solubility, high drug loading (31.60% ± 2.85), encapsulation efficiency (60.52% ± 2.79), and minimal side effects. Furthermore, CEL@ZIF-8@PEG-BIO can release chemicals in response to an acidic micro-environment, which is more likely a tumor micro-environment. In vitro, studies showed that CEL@ZIF-8@BIO inhibited cell proliferation, led to mitochondrial membrane potential (MMP) decline, and generated reactive oxygen species in OC cells. Both in vitro and in vivo experiments indicated that CEL@ZIF-8@PEG-BIO enhanced anti-tumor activity against OC via up-regulated apoptosis-promoting biomarkers and rendered cancer cell apoptosis via the P38/JNK MAPK signaling pathway. In conclusion, we have successfully developed a novel drug delivery system (CEL@ZIF-8@PEG-BIO), resulting in significant improvements in both water solubility and anti-tumor efficacy thereby providing valuable insights for future clinical drug development.
KW - Ovarian cancer
KW - Celastrol
KW - Zeolitic imidazolate framework-8
KW - Anti-tumor
KW - Biotin
UR - http://www.scopus.com/inward/record.url?scp=85172155558&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2023.115573
DO - 10.1016/j.biopha.2023.115573
M3 - Journal article
AN - SCOPUS:85172155558
SN - 0753-3322
VL - 167
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 115573
ER -
