Active targeting co-delivery of therapeutic siRNAs and antineoplastic drugs is considered as a very promising approach to specifically improve the therapeutic effect by simultaneously inhibiting the expression of tumorigenic genes and reducing the systemic toxicity of anticancer drugs. This strategy for effectively targeting cancer stem cells (CSCs) has gained considerable attention in the therapeutic treatment of human cancers. The objective of this study was to fabricate and characterize the therapeutic survivin siRNAs (Sur siRNA) and anti-cancer drug doxorubicin (DOX)-loaded superparamagnetic iron oxide nanoparticles (SPIONPs) that are surface-conjugated to the specific ligand epidermal growth factor receptor (EGFR) which is highly expressed on brain glioblastoma stem cells (GSCs), using carboxymethyl chitosan (CMCS), polyethylenimine (PEI) and heparin-mediated cross linking agents. Our in vitro and in vivo studies demonstrated that the fabricated EGFR-targeted nanoparticles exhibited excellent targeting specificity and enhanced delivery efficiency, and could specifically co-deliver therapeutic siRNAs and DOX into GSCs, thus greatly improving the therapeutic efficacy by effectively silencing survivin gene expression and enhancing the treatment sensitivity of GSCs to anticancer drug DOX. Therefore, these fabricated EGFR-targeted nanoparticles would provide an efficient targeting vector for co-delivery of therapeutic siRNAs and anticancer drugs, and could be used as a promising active targeted nanocarrier for the selective treatment of human brain cancer in the future.

中文翻译：

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通过表皮生长因子受体介导的磁性纳米粒子主动靶向治疗性Sur siRNA和抗肿瘤药物的共同靶向递送，以在胶质母细胞瘤干细胞中协同程序性细胞死亡

活性靶向治疗性siRNA和抗肿瘤药的共同递送被认为是通过同时抑制致癌基因的表达并降低抗癌药的系统毒性来特异性提高治疗效果的非常有前途的方法。在人类癌症的治疗中，有效靶向癌症干细胞（CSCs）的这一策略已引起广泛关注。这项研究的目的是制造和表征治疗性survivin siRNA（SursiRNA）和负载抗癌药阿霉素（DOX）的超顺磁性氧化铁纳米颗粒（SPIONPs）表面偶联至在脑胶质母细胞瘤干细胞（GSC）上高度表达的特定配体表皮生长因子受体（EGFR）羧甲基壳聚糖（CMCS），聚乙烯亚胺（PEI）和肝素介导的交联剂。我们的体外和体内研究表明，制备的靶向EGFR的纳米颗粒表现出出色的靶向特异性和更高的递送效率，并且可以将治疗性siRNA和DOX特异性共递送至GSC中，从而通过有效沉默survivin大大提高了治疗效果。基因表达并增强GSC对抗癌药DOX的治疗敏感性。因此，这些制备的靶向EGFR的纳米粒子将为共递送治疗性siRNA和抗癌药物提供有效的靶向载体，并可在将来用作选择性治疗人脑癌的有希望的活性靶向纳米载体。