Targeted combination therapy has shown promise to achieve maximum therapeutic efficacy by overcoming drug resistance. MicroRNA-21 (miR-21) is frequently overexpressed in various cancer types including breast and non-small cell lung cancer and its functions can be inhibited by miR inhibitor (miR-21i). A combination of miR-21i and a chemo drug, doxorubicin (Dox), can provide synergistic effects. Here, we developed a calcium phosphate (CaP)-coated nanoparticle (NP) formulation to co-deliver miR-21i along with Dox. This NP design can be used to deliver the two agents with different physiochemical properties. The NP formulation was optimized for particle size, polydispersity, Dox loading, and miR-21i loading. The NP formulation was confirmed to downregulate miR-21 levels and upregulate tumor suppressor gene levels. The cytotoxic efficacy of the combined miR-21i and Dox-containing NPs was found to be higher than that of Dox. Therefore, the CaP-coated hybrid lipid-polymeric NPs hold potential for the delivery of miR-21i and Dox.

靶向联合治疗已显示出通过克服耐药性来实现最大治疗效果的希望。MicroRNA-21 (miR-21) 在包括乳腺癌和非小细胞肺癌在内的各种癌症类型中经常过度表达，其功能可以被 miR 抑制剂 (miR-21i) 抑制。miR-21i 和化疗药物阿霉素 (Dox) 的组合可以提供协同效应。在这里，我们开发了一种磷酸钙 (CaP) 包被的纳米颗粒 (NP) 配方，以与 Dox 共同递送 miR-21i。这种 NP 设计可用于递送具有不同理化特性的两种药剂。NP 配方针对粒径、多分散性、Dox 负载和 miR-21i 负载进行了优化。证实 NP 制剂可下调 miR-21 水平并上调肿瘤抑制基因水平。发现组合的 miR-21i 和含 Dox 的 NPs 的细胞毒性功效高于 Dox。因此，CaP 包被的混合脂质聚合物 NPs 具有传递 miR-21i 和 Dox 的潜力。