Maurer Viktor, Altin Selin, Ag Seleci Didem, Zarinwall Ajmal, Temel Bilal, Vogt Peter M, Strauß Sarah, Stahl Frank, Scheper Thomas, Bucan Vesna, Garnweitner Georg
Institute for Particle Technology, Technische Universität Braunschweig, 38104 Braunschweig, Germany.
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, 38106 Braunschweig, Germany.
Pharmaceutics. 2021 Mar 16;13(3):394. doi: 10.3390/pharmaceutics13030394.
Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FeO-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
尽管像厄洛替尼这样的化疗药物在临床上已被确立用于治疗乳腺癌，但利用RNA干扰（RNAi）机制进行联合治疗可极大提高其疗效和治疗效果。然而，单纯的小干扰RNA（siRNA）细胞摄取不足，且其在血液中快速降解导致递送不足，无法在靶组织内实现合适的积累。为解决这些问题，非离子表面活性剂囊泡（niosomes）被用作纳米载体平台，将Lifeguard（LFG）特异性siRNA包裹在亲水核内。为通过外部磁操纵增强细胞摄取，此前已在niosomal双层结构内包封超顺磁性氧化铁纳米颗粒（FeO-NPs）。在验证siRNA的高效包封后，将所得的混合niosomes与厄洛替尼或曲妥珠单抗联合用于BT-474细胞治疗，并监测诱导的细胞凋亡情况。获得的结果表明，纳米载体成功导致BT-474细胞中LFG基因下调，与单纯添加siRNA相比，这提高了化疗药物的疗效。特别是外部磁场的应用增强了siRNA的内化，从而增加了凋亡信号通路的激活。考虑到治疗效果的改善以及高包封效率，所制备的混合niosomes符合经济高效商业化的要求，可被视为未来siRNA递送剂的有前景的候选者。
