Sharifiaghdam Maryam, Shaabani Elnaz, Sharifiaghdam Zeynab, De Keersmaecker Herlinde, De Rycke Riet, De Smedt Stefaan, Faridi-Majidi Reza, Braeckmans Kevin, Fraire Juan C
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium.
Front Mol Biosci. 2021 Apr 20;8:639184. doi: 10.3389/fmolb.2021.639184. eCollection 2021.
Nanotechnology has made an important contribution to oncology in recent years, especially for drug delivery. While many different nano-delivery systems have been suggested for cancer therapy, selenium nanoparticles (SeNPs) are particularly promising anticancer drug carriers as their core material offers interesting synergistic effects to cancer cells. Se compounds can exert cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis, eventually leading to apoptosis induction in many kinds of cancer cells. Herein, we report on the design and synthesis of novel layer-by-layer Se-based nanocomplexes (LBL-Se-NCs) as carriers of small interfering RNA (siRNA) for combined gene silencing and apoptosis induction in cancer cells. The LBL-Se-NCs were prepared using a straightforward electrostatic assembly of siRNA and chitosan (CS) on the solid core of the SeNP. In this study, we started by investigating the colloidal stability and protection of the complexed siRNA. The results show that CS not only functioned as an anchoring layer for siRNA, but also provided colloidal stability for at least 20 days in different media when CS was applied as a third layer. The release study revealed that siRNA remained better associated with LBL-Se-NCs, with only a release of 35% after 7 days, as compared to CS-NCs with a siRNA release of 100% after 48 h, making the LBL nanocarrier an excellent candidate as an off-the-shelf formulation. When applied to H1299 cells, it was found that they can selectively induce around 32% apoptosis, while significantly less apoptosis (5.6%) was induced in NIH/3T3 normal cells. At the same time, they were capable of efficiently inducing siRNA downregulation (35%) without loss of activity 7 days post-synthesis. We conclude that LBL-Se-NCs are promising siRNA carriers with enhanced stability and with a dual mode of action against cancer cells.
近年来，纳米技术在肿瘤学领域做出了重要贡献，尤其是在药物递送方面。虽然已经提出了许多不同的纳米递送系统用于癌症治疗，但硒纳米颗粒（SeNP）作为抗癌药物载体特别有前景，因为其核心材料对癌细胞具有有趣的协同作用。硒化合物可以通过作为改变细胞氧化还原稳态的促氧化剂发挥细胞毒性作用，最终导致多种癌细胞凋亡。在此，我们报告了新型逐层硒基纳米复合物（LBL-Se-NC）的设计与合成，该复合物作为小干扰RNA（siRNA）的载体，用于癌细胞中的联合基因沉默和凋亡诱导。LBL-Se-NC是通过在SeNP的固体核心上直接进行siRNA和壳聚糖（CS）的静电组装制备的。在本研究中，我们首先研究了复合siRNA的胶体稳定性和保护作用。结果表明，CS不仅作为siRNA的锚定层，而且当CS作为第三层应用时，在不同介质中可提供至少20天的胶体稳定性。释放研究表明，siRNA与LBL-Se-NC的结合更好，7天后仅释放35%，而CS-NC在48小时后siRNA释放率为100%，这使得LBL纳米载体成为现成制剂的优秀候选者。当应用于H1299细胞时，发现它们可以选择性地诱导约32%的细胞凋亡，而在NIH/3T3正常细胞中诱导的细胞凋亡明显较少（5.6%）。同时，它们能够在合成后7天有效地诱导siRNA下调（35%）且不失活。我们得出结论，LBL-Se-NC是有前景的siRNA载体，具有增强的稳定性和对癌细胞的双重作用模式。
