• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

脂质体共递送齐墩果酸减轻阿霉素诱导的肝细胞癌多器官毒性。

Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma.

作者信息

Sarfraz Muhammad, Afzal Attia, Raza Shahid Masood, Bashir Sajid, Madni Asadullah, Khan Muhammad Waseem, Ma Xiang, Xiang Guangya

机构信息

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Department of Pharmacy, University of Sargodha, Sargodha, 40100, Punjab, Pakistan.

出版信息

Oncotarget. 2017 Jul 18;8(29):47136-47153. doi: 10.18632/oncotarget.17559.

DOI:10.18632/oncotarget.17559
PMID:28525367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5564550/
Abstract

Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA- and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.

摘要

阿霉素与其他细胞毒性药物联合使用具有临床优势。然而，阿霉素诱导的心脏毒性对临床应用和治疗结果产生负面影响。心脏毒性可能源于氧化应激增加或局部细胞色素P450介导的20-羟基-5,8,11,14-二十碳四烯酸（20-HETE）增加。齐墩果酸（OA）是一种天然的五环三萜类化合物，具有自由基清除、心脏保护和P450介导的环氧化酶上调特性。我们在肝癌（HCC）的HepG2模型中研究了脂质体OA和阿霉素的共递送。OA减轻了阿霉素诱导的心脏毒性，同时不影响其抗癌活性。凋亡分析表明，DOX和OA的共递送产生了协同抗癌作用。然而，这两种药物对心肌细胞有拮抗作用。用载有OA和DOX的脂质体（ODLs）处理的雌性BALB/c裸鼠表现出肿瘤生长减少、体重稳定和器官指数稳定。20-HETE生成减少表明ODLs的心脏毒性有限。在用ODLs处理的小鼠中未观察到生化或组织病理学标志物的变化。因此，OA和DOX的定制共递送可能是治疗HCC的一种有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/8c3b18fd52e2/oncotarget-08-47136-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/7c7fd1b269ee/oncotarget-08-47136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/99374380a803/oncotarget-08-47136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/e83d7a0d3442/oncotarget-08-47136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/c254ac4d5df2/oncotarget-08-47136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/7dd6cb7ddd38/oncotarget-08-47136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/21b6a9c0e197/oncotarget-08-47136-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/3f72940c89a9/oncotarget-08-47136-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/d603ede921bf/oncotarget-08-47136-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/1ac887bb5540/oncotarget-08-47136-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/5502b512314a/oncotarget-08-47136-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/8c3b18fd52e2/oncotarget-08-47136-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/7c7fd1b269ee/oncotarget-08-47136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/99374380a803/oncotarget-08-47136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/e83d7a0d3442/oncotarget-08-47136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/c254ac4d5df2/oncotarget-08-47136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/7dd6cb7ddd38/oncotarget-08-47136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/21b6a9c0e197/oncotarget-08-47136-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/3f72940c89a9/oncotarget-08-47136-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/d603ede921bf/oncotarget-08-47136-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/1ac887bb5540/oncotarget-08-47136-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/5502b512314a/oncotarget-08-47136-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada8/5564550/8c3b18fd52e2/oncotarget-08-47136-g011.jpg

相似文献

1
Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma.脂质体共递送齐墩果酸减轻阿霉素诱导的肝细胞癌多器官毒性。
Oncotarget. 2017 Jul 18;8(29):47136-47153. doi: 10.18632/oncotarget.17559.
2
Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity.载顺铂-齐墩果酸碳酸钙纳米粒对肝癌细胞的协同作用增强凋亡，降低肝毒性。
Int J Nanomedicine. 2019 May 28;14:3753-3771. doi: 10.2147/IJN.S196651. eCollection 2019.
3
Ellagic acid synergistically potentiates inhibitory activities of chemotherapeutic agents to human hepatocellular carcinoma.鞣花酸协同增强化疗药物对人肝癌细胞的抑制活性。
Phytomedicine. 2019 Jun;59:152921. doi: 10.1016/j.phymed.2019.152921. Epub 2019 Apr 4.
4
Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes.通过 CD147 抗体偶联免疫脂质体增强多柔比星向肝癌细胞的递送。
Nanomedicine. 2018 Aug;14(6):1949-1961. doi: 10.1016/j.nano.2017.09.012. Epub 2017 Oct 16.
5
Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity.适配体-药物偶联物：在HER3适配体功能化脂质体递送系统中靶向递送阿霉素可降低心脏毒性。
Int J Nanomedicine. 2018 Feb 5;13:763-776. doi: 10.2147/IJN.S149887. eCollection 2018.
6
Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice.多柔比星和维拉帕米载入壳聚糖纳米粒共同处理对二乙基亚硝胺诱导的小鼠肝癌的影响。
Hum Exp Toxicol. 2020 Nov;39(11):1528-1544. doi: 10.1177/0960327120930266. Epub 2020 Jun 10.
7
Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo.由齐墩果酸制成的多囊泡脂质体控释给药系统对体外和体内肝细胞癌的作用
Int J Nanomedicine. 2016 Jul 12;11:3111-29. doi: 10.2147/IJN.S108445. eCollection 2016.
8
Low-toxicity transferrin-guided polymersomal doxorubicin for potent chemotherapy of orthotopic hepatocellular carcinoma in vivo.低毒性转铁蛋白导向聚合物胶束阿霉素用于体内原位肝癌的强效化疗。
Acta Biomater. 2019 Jul 1;92:196-204. doi: 10.1016/j.actbio.2019.05.034. Epub 2019 May 15.
9
A novel self-assembly albumin nanocarrier for reducing doxorubicin-mediated cardiotoxicity.一种新型自组装白蛋白纳米载体，用于降低阿霉素介导的心脏毒性。
J Pharm Sci. 2013 May;102(5):1626-35. doi: 10.1002/jps.23455. Epub 2013 Feb 19.
10
Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model.局部超声靶向微泡破坏联合阿霉素脂质体在H22小鼠肝癌模型中的有效性
J Drug Target. 2015 May;23(4):323-34. doi: 10.3109/1061186X.2014.996759. Epub 2015 Jan 22.

引用本文的文献

1
Application of Nanotechnology in TACE Treatment of Liver Cancer.纳米技术在肝癌经动脉化疗栓塞治疗中的应用
Int J Nanomedicine. 2025 Aug 4;20:9621-9639. doi: 10.2147/IJN.S527518. eCollection 2025.
2
Tetrahedral Framework Nucleic Acids Inhibit Oxidative Stress and Cardiomyocyte Apoptosis in Doxorubicin-Induced Cardiotoxicity.四面体框架核酸抑制阿霉素诱导的心脏毒性中的氧化应激和心肌细胞凋亡。
Int J Nanomedicine. 2025 Jul 21;20:9275-9289. doi: 10.2147/IJN.S529346. eCollection 2025.
3
Exploring the therapeutic potential of oleanolic acid and its derivatives in cancer treatment: a comprehensive review.

本文引用的文献

1
Inhibition of cancer antioxidant defense by natural compounds.天然化合物对癌症抗氧化防御的抑制作用。
Oncotarget. 2017 Feb 28;8(9):15996-16016. doi: 10.18632/oncotarget.13723.
2
Combination treatment including targeted therapy for advanced hepatocellular carcinoma.包括针对晚期肝细胞癌的靶向治疗在内的联合治疗。
Oncotarget. 2016 Oct 25;7(43):71036-71051. doi: 10.18632/oncotarget.11954.
3
Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo.
探索齐墩果酸及其衍生物在癌症治疗中的治疗潜力：一项综合综述。
3 Biotech. 2025 Mar;15(3):56. doi: 10.1007/s13205-025-04209-5. Epub 2025 Feb 7.
4
Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer.天然抗氧化剂的纳米制剂治疗肝癌。
Biomolecules. 2024 Aug 19;14(8):1031. doi: 10.3390/biom14081031.
5
Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting.阿霉素制剂在增强药代动力学和肿瘤靶向性方面的最新进展
Pharmaceuticals (Basel). 2023 May 29;16(6):802. doi: 10.3390/ph16060802.
6
Natural Compounds: Co-Delivery Strategies with Chemotherapeutic Agents or Nucleic Acids Using Lipid-Based Nanocarriers.天然化合物：使用基于脂质的纳米载体与化疗药物或核酸的共递送策略
Pharmaceutics. 2023 Apr 21;15(4):1317. doi: 10.3390/pharmaceutics15041317.
7
Hybrid Lipid Nanoformulations for Hepatoma Therapy: Sorafenib Loaded Nanoliposomes-A Preliminary Study.用于肝癌治疗的混合脂质纳米制剂：载有索拉非尼的纳米脂质体——一项初步研究
Nanomaterials (Basel). 2022 Aug 17;12(16):2833. doi: 10.3390/nano12162833.
8
3,5,3'-Triiodothyronine-Loaded Liposomes Inhibit Hepatocarcinogenesis Inflammation-Associated Macrophages.载有3,5,3'-三碘甲状腺原氨酸的脂质体抑制肝癌发生过程中与炎症相关的巨噬细胞。
Front Oncol. 2022 May 10;12:877982. doi: 10.3389/fonc.2022.877982. eCollection 2022.
9
Reparative Efficacy of Liposome-Encapsulated Oleanolic Acid against Liver Inflammation Induced by Fine Ambient Particulate Matter and Alcohol in Mice.脂质体包裹齐墩果酸对小鼠环境细颗粒物和酒精诱导的肝脏炎症的修复作用
Pharmaceutics. 2022 May 23;14(5):1108. doi: 10.3390/pharmaceutics14051108.
10
Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances.基于脂质的纳米颗粒作为一种新型的肝细胞癌治疗方法：靶向和最新进展的综合综述。
J Nanobiotechnology. 2022 Mar 5;20(1):109. doi: 10.1186/s12951-022-01309-9.
由齐墩果酸制成的多囊泡脂质体控释给药系统对体外和体内肝细胞癌的作用
Int J Nanomedicine. 2016 Jul 12;11:3111-29. doi: 10.2147/IJN.S108445. eCollection 2016.
4
Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region.亚太地区肝细胞癌的流行病学
Gut Liver. 2016 May 23;10(3):332-9. doi: 10.5009/gnl15257.
5
Remote loading of doxorubicin into liposomes by transmembrane pH gradient to reduce toxicity toward H9c2 cells.通过跨膜pH梯度将阿霉素远程装载到脂质体中以降低对H9c2细胞的毒性。
Saudi Pharm J. 2016 Mar;24(2):165-75. doi: 10.1016/j.jsps.2015.02.014. Epub 2015 Mar 14.
6
Self-assembly and cytotoxicity study of PEG-modified ursolic acid liposomes.聚乙二醇修饰熊果酸脂质体的自组装及细胞毒性研究。
Mater Sci Eng C Mater Biol Appl. 2015 Aug;53:196-203. doi: 10.1016/j.msec.2015.04.022. Epub 2015 Apr 22.
7
Simple amides of oleanolic acid as effective penetration enhancers.齐墩果酸的简单酰胺作为有效的渗透促进剂。
PLoS One. 2015 May 26;10(5):e0122857. doi: 10.1371/journal.pone.0122857. eCollection 2015.
8
PEGylated cationic nanoemulsions can efficiently bind and transfect pIDUA in a mucopolysaccharidosis type I murine model.聚乙二醇化阳离子纳米乳能够有效地结合并转染黏多糖贮积症 I 型小鼠模型中的 pIDUA。
J Control Release. 2015 Jul 10;209:37-46. doi: 10.1016/j.jconrel.2015.04.013. Epub 2015 Apr 14.
9
Advances and challenges in the use of nanoparticles to optimize PK/PD interactions of combined anti-cancer therapies.使用纳米颗粒优化联合抗癌疗法的药代动力学/药效学相互作用的进展与挑战。
Curr Drug Metab. 2014;15(8):818-28. doi: 10.2174/1389200216666150223152958.
10
A novel oleanolic acid-loaded PLGA-TPGS nanoparticle for liver cancer treatment.一种用于肝癌治疗的新型负载齐墩果酸的聚乳酸-羟基乙酸共聚物-维生素E聚乙二醇琥珀酸酯纳米粒。
Drug Dev Ind Pharm. 2015;41(7):1193-203. doi: 10.3109/03639045.2014.938081. Epub 2014 Jul 15.