Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy
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 utmo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223013719 |
| _version_ | 1797660514479767552 |
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| author | Ruisi Zhou Yanting You Zhiqiang Zha Jie Chen Yanchun Li Xiaohu Chen Xiaomei Chen Xuefeng Jiang Jinxiang Chen Hiu Yee Kwan Xiaoshan Zhao Liping Huang Yanyan Liu |
| author_facet | Ruisi Zhou Yanting You Zhiqiang Zha Jie Chen Yanchun Li Xiaohu Chen Xiaomei Chen Xuefeng Jiang Jinxiang Chen Hiu Yee Kwan Xiaoshan Zhao Liping Huang Yanyan Liu |
| author_sort | Ruisi Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:32:01Z |
| format | Article |
| id | doaj.art-79fcc27441844825ae8e2ce0e2d0db92 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:32:01Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-79fcc27441844825ae8e2ce0e2d0db922023-10-13T11:03:11ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115573Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapyRuisi Zhou0Yanting You1Zhiqiang Zha2Jie Chen3Yanchun Li4Xiaohu Chen5Xiaomei Chen6Xuefeng Jiang7Jinxiang Chen8Hiu Yee Kwan9Xiaoshan Zhao10Liping Huang11Yanyan Liu12Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authors.Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authors.School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S0753332223013719Ovarian cancerCelastrolZeolitic imidazolate framework-8Anti-tumorBiotin |
| spellingShingle | Ruisi Zhou Yanting You Zhiqiang Zha Jie Chen Yanchun Li Xiaohu Chen Xiaomei Chen Xuefeng Jiang Jinxiang Chen Hiu Yee Kwan Xiaoshan Zhao Liping Huang Yanyan Liu Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy Biomedicine & Pharmacotherapy Ovarian cancer Celastrol Zeolitic imidazolate framework-8 Anti-tumor Biotin |
| title | Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy |
| title_full | Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy |
| title_fullStr | Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy |
| title_full_unstemmed | Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy |
| title_short | Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy |
| title_sort | biotin decorated celastrol loaded zif 8 nano drug delivery system targeted epithelial ovarian cancer therapy |
| topic | Ovarian cancer Celastrol Zeolitic imidazolate framework-8 Anti-tumor Biotin |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223013719 |
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