Exploring the anti-myeloma potential of composite nanoparticles As4S4/Fe3O4: Insights from in vitro, ex vivo and in vivo studies

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-08-05 DOI:10.1016/j.nano.2024.102777

{"title":"Exploring the anti-myeloma potential of composite nanoparticles As4S4/Fe3O4: Insights from in vitro, ex vivo and in vivo studies","authors":"","doi":"10.1016/j.nano.2024.102777","DOIUrl":null,"url":null,"abstract":"<div>Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As4S4/Fe3O4 (4:1) and As4S4/Fe3O4 (1:1) demonstrated effective anti-MM activity in in vitro, ex vivo, and in vivo in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G2/M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As4S4/Fe3O4 (4:1) observed synergism with dexamethasone and melphalan, while As4S4/Fe3O4 (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM.</div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000467/pdfft?md5=b83c7b1c404c8c4762085cf98d2dfb2d&pid=1-s2.0-S1549963424000467-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963424000467","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As₄S₄/Fe₃O₄ (4:1) and As₄S₄/Fe₃O₄ (1:1) demonstrated effective anti-MM activity in in vitro, ex vivo, and in vivo in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G₂/M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As₄S₄/Fe₃O₄ (4:1) observed synergism with dexamethasone and melphalan, while As₄S₄/Fe₃O₄ (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM.

Abstract Image

查看原文本刊更多论文

探索 As4S4/Fe3O4 复合纳米粒子的抗骨髓瘤潜力：体外、体内和体外研究的启示。

鉴于多发性骨髓瘤（MM）在恶性浆细胞（PCs）克隆增殖方面的深刻异质性和纳米疗法的抗MM治疗潜力，为MM患者制定治疗方案势在必行。As4S4/Fe3O4（4:1）和As4S4/Fe3O4（1:1）这两种复合纳米粒子（NPs）在体外、体内和异种移植小鼠模型中均显示出有效的抗MM活性。复合氧化萘引发了p-ERK1/2/p-JNK的激活，c-Myc、p-PI3K、p-4E-BP1的下调；G2/M细胞周期停滞，细胞周期蛋白B1、组蛋白H2AX/H3增加，p-ATR、p-Chk1/p-Chk2、p-H2AX/p-H3激活；以及树突酶和线粒体依赖性凋亡诱导。无论是单独使用还是在基质存在的情况下，NPs都能减少MM细胞中的干细胞样侧群。为了获得更高的临床反应率，As4S4/Fe3O4（4:1）与地塞米松和美法仑协同作用，而As4S4/Fe3O4（1:1）与硼替佐米、来那度胺和泊马度胺等抗MM药物联用则显示出协同效应，这为在MM中进一步临床评估复合纳米粒子提供了框架。

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分钟内获得全文求助全文

来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.