Doxorubicin-loaded PEG-CdTe QDs conjugated with anti-CXCR4 mAbs: a novel delivery system for extramedullary multiple myeloma treatment

IF 4.2 3区医学 Q2 ENGINEERING, BIOMEDICAL Journal of Materials Science: Materials in Medicine Pub Date : 2024-01-20 DOI:10.1007/s10856-023-06772-w

Dangui Chen, Fei Chen, Jia Lu, Lihong Wang, Fusheng Yao, Haitao Xu

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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.

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多柔比星负载型 PEG-CdTe QDs 与抗 CXCR4 mAbs 共轭：治疗髓外多发性骨髓瘤的新型递送系统

摘要髓外多发性骨髓瘤（EMM）是指多发性骨髓瘤患者骨髓外出现浆细胞，其预后较差。大剂量化疗联合自体干细胞移植作为早期治疗的一个不错选择，保留了髓外多发性骨髓瘤患者的生存优势，但由于药物的细胞毒性，大多数老年患者无法耐受。为了从根本上解决上述不耐受问题，我们设计了一种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：多柔比星）纳米平台。首先，CXCR4 在髓外浆细胞中高度表达。其次，PEG-CdTe 是一种药物载体，可控制药物释放，减少不良反应，延长药物（如 DOX）在体内的循环时间，并在连接抗体后形成靶向载体。体外实验表明，CXCR4-PEG-CdTe-DOX 通过主动的 CXCR4 靶向作用促进药物在细胞内蓄积，并以 pH 值可控的方式将 DOX 释放到微环境中，提高了疗效和骨髓瘤细胞（U266）的凋亡率。因此，由CXCR4-PEG-CdTe-DOX介导的靶向化疗是EMM治疗的一个很有前景的选择。

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来源期刊

Journal of Materials Science: Materials in Medicine 工程技术-材料科学：生物材料

CiteScore

8.00

自引率

0.00%

发文量

审稿时长

3.5 months

期刊介绍： The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.