Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.
机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, People's Republic of China.[2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.[3]Huidong County Maternal and Child Health Service Center, Huizhou 516300, People's Republic of China.[4]The Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.[5]School of Forensic Medicine, Southern Medical University, Guangzhou 510515, People's Republic of China.
Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.
基金：
This work was supported by grants from the National Natural
Science Foundation of China (Grant Nos. 51903119,
51773198), Guangzhou Science and Technology Bureau
(202206010068), and China Postdoctoral Science Foundation
(Grant No. 2020M672543).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|3 区工程技术
小类|3 区材料科学：生物材料
最新[2025]版：
大类|3 区医学
小类|3 区材料科学：生物材料
第一作者：
第一作者机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, People's Republic of China.[2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
通讯作者：
通讯机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, People's Republic of China.[2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
推荐引用方式(GB/T 7714)：
Luo Zhijian,Luo Yantao,Liang Xiaoling,et al.Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.[J].ACS biomaterials science & engineering.2022,doi:10.1021/acsbiomaterials.2c00316.
APA：
Luo Zhijian,Luo Yantao,Liang Xiaoling,Lyu Qingyang,Meng Fanliang...&Zhou Dongfang.(2022).Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway..ACS biomaterials science & engineering,,
MLA：
Luo Zhijian,et al."Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.".ACS biomaterials science & engineering .(2022)
