Abstract

Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.

Graphical abstract

中文翻译：

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负载阿霉素的 PEG-CdTe QD 与抗 CXCR4 mAb 缀合：一种用于髓外多发性骨髓瘤治疗的新型递送系统

摘要

髓外多发性骨髓瘤（EMM）被定义为多发性骨髓瘤患者骨髓外存在浆细胞，其预后较差。高剂量化疗联合自体干细胞移植作为早期治疗的一个不错的选择，保留了年轻EMM患者的生存获益，但由于药物细胞毒性而对大多数老年患者不耐受。为了从根本上解决上述不耐受问题，我们设计了CXCR4-PEG-CdTe-DOX（其中CXCR4：趋化因子受体4；PEG-CdTe：聚乙二醇修饰的碲化镉；DOX：阿霉素）纳米平台。首先，CXCR4在髓外浆细胞中高表达。其次，PEG-CdTe作为控制药物释放的药物载体，可以减少不良反应，延长药物（如DOX）在体内的循环时间，连接抗体后形成靶向载体。体外实验表明，CXCR4-PEG-CdTe-DOX通过主动CXCR4靶向促进细胞内药物积累，并以pH控制的方式将DOX释放到微环境中，提高骨髓瘤细胞（U266）的治疗效果和凋亡率。因此，CXCR4-PEG-CdTe-DOX介导的靶向化疗是EMM治疗的一个有前景的选择。

图形概要