Self-assembled nanoparticles of alginate and paclitaxel-triphenylphosphonium for mitochondrial apoptosis targeting.

IF 2.8 4区 医学 Q2 ONCOLOGY Medical Oncology Pub Date : 2024-10-24 DOI:10.1007/s12032-024-02540-0
Mehdi Esfandyari-Manesh, Bahar Morshedi, Parisa Joolaie, Rassoul Dinarvand
{"title":"Self-assembled nanoparticles of alginate and paclitaxel-triphenylphosphonium for mitochondrial apoptosis targeting.","authors":"Mehdi Esfandyari-Manesh, Bahar Morshedi, Parisa Joolaie, Rassoul Dinarvand","doi":"10.1007/s12032-024-02540-0","DOIUrl":null,"url":null,"abstract":"<p><p>Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around - 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"41 12","pages":"299"},"PeriodicalIF":2.8000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12032-024-02540-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around - 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
用于线粒体凋亡靶向的海藻酸盐和紫杉醇-三苯基膦自组装纳米颗粒。
紫杉醇(PTX)是紫杉类药物中的一种抗有丝分裂药物,它通过抑制有丝分裂和激活一连串信号通路来阻止乳腺癌细胞的增殖,从而导致细胞凋亡。线粒体是诱导细胞凋亡的重要信号途径之一。为实现线粒体靶向,三苯基膦(TPP)具有电荷分散和疏水性,可作为分子促进穿透线粒体磷脂膜。PTX-TPP 是通过 PTX 的羟基和(4-羧基丁基)TPP 的羧酸之间的 pH 敏感酯键合成的。然后将 PTX-TPP 原药包封在海藻酸盐纳米颗粒中,利用离子络合技术自组装成增强乳腺癌细胞线粒体凋亡的纳米颗粒。在自组装的海藻酸盐纳米颗粒中,PTX-TPP 共轭物的负载量为 16.5%,纳米颗粒的粒径为 123 nm,zeta 电位约为 - 25.8 Mv。PTX-TPP 纳米粒子对 MCF7 癌细胞生长的体外细胞毒性和 IC50 值比游离 PTX 高 6.3 倍。PTX-TPP 纳米粒子的早期凋亡细胞和晚期凋亡/坏死细胞分别比游离 PTX 高 11.6 倍和 3.9 倍。这项研究表明,这种线粒体靶向自组装纳米粒子可以抑制乳腺癌肿瘤细胞的生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
期刊最新文献
An overview on the interaction between non-coding RNAs and CTLA-4 gene in human diseases. Exploring the role of antigen-presenting cancer-associated fibroblasts and CD74 on the pancreatic ductal adenocarcinoma tumor microenvironment. Telomerase inhibition in breast cancer and breast cancer stem cells: a brief review. N6-methyladenosine RNA modification in head and neck squamous cell carcinoma (HNSCC): current status and future insights. Dual roles of extracellular vesicles in acute lymphoblastic leukemia: implications for disease progression and theranostic strategies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1