Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy

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

doi:10.1016/j.biopha.2023.115573

Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy

Biomed Pharmacother. 2023 Nov:167:115573. doi: 10.1016/j.biopha.2023.115573. Epub 2023 Sep 26.

Authors

Ruisi Zhou¹, Yanting You², Zhiqiang Zha³, Jie Chen², Yanchun Li², Xiaohu Chen², Xiaomei Chen², Xuefeng Jiang², Jinxiang Chen⁴, Hiu Yee Kwan⁵, Xiaoshan Zhao⁶, Liping Huang⁷, Yanyan Liu⁸

Affiliations

¹ Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
² School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
³ Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
⁴ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
⁵ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
⁶ School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: zhaoxs0609@163.com.
⁷ Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: lphuang2006@126.com.
⁸ School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: 799042406@qq.com.

PMID: 37769391
DOI: 10.1016/j.biopha.2023.115573

Abstract

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.

Keywords: Anti-tumor; Biotin; Celastrol; Ovarian cancer; Zeolitic imidazolate framework-8.