鉴于恶性浆细胞（PC）克隆增殖的多发性骨髓瘤（MM）显着异质性和纳米疗法的抗MM治疗潜力，为MM患者制定治疗方案是不可避免的。两种复合纳米颗粒 (NP) As4S4/Fe3O4 (4:1) 和 As4S4/Fe3O4 (1:1) 在异种移植小鼠模型的体外、离体和体内均表现出有效的抗 MM 活性。复合纳米粒子触发 p-ERK1/2/p-JNK 激活，并下调 c-Myc、p-PI3K、p-4E-BP1； 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；以及半胱天冬酶和线粒体依赖性细胞凋亡诱导。无论是单独使用还是在基质存在的情况下，NP 都会减弱 MM 细胞中的干细胞样侧群。为了获得更高的临床缓解率，As4S4/Fe3O4 (4:1) 观察到与地塞米松和美法仑的协同作用，而 As4S4/Fe3O4 (1:1) 与硼替佐米、来那度胺和泊马度胺抗 MM 药物联合显示出协同作用，提供了框架用于对 MM 中的复合 NP 进行进一步的临床评估。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.