Xiao Shili, Castro Rita, Maciel Dina, Gonçalves Mara, Shi Xiangyang, Rodrigues João, Tomás Helena
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073, People's Republic of China; CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal.
CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal.
Mater Sci Eng C Mater Biol Appl. 2016 Mar;60:348-356. doi: 10.1016/j.msec.2015.11.051. Epub 2015 Dec 1.
Despite the wide research done in the field, the development of advanced drug delivery systems with improved drug delivery properties and effective anticancer capability still remains a great challenge. Based on previous work that showed the potentialities of the nanoclay Laponite as a pH-sensitive doxorubicin (Dox) delivery vehicle, herein we report a simple method to modulate its extent of drug release at different pH values. This was achieved by alternate deposition of cationic poly(allylamine) hydrochloride and anionic poly(sodium styrene sulfonate) (PAH/PSS) polyelectrolytes over the surface of Dox-loaded Laponite nanoparticles using the electrostatic layer-by-layer (LbL) self-assembly approach. The successful formation of polyelectrolyte multilayer-coated Dox/Laponite systems was confirmed by Dynamic Light Scattering and zeta potential measurements. Systematic studies were performed to evaluate their drug release profiles and anticancer efficiency. Our results showed that the presence of the polyelectrolyte multilayers improved the sustained release properties of Laponite and allowed a fine tuning of the extension of drug release at neutral and acidic pH values. The cytotoxicity presented by polyelectrolyte multilayer-coated Dox/Laponite systems towards MCF-7 cells was in accordance with the drug delivery profiles. Furthermore, cellular uptake studies revealed that polyelectrolyte multilayer-coated Dox/Laponite nanoparticles can be effectively internalized by cells conducting to Dox accumulation in cell nucleus.
尽管在该领域已开展了广泛研究，但开发具有改善的药物递送特性和有效抗癌能力的先进药物递送系统仍然是一项巨大挑战。基于先前显示纳米粘土锂皂石作为pH敏感型阿霉素（Dox）递送载体潜力的工作，在此我们报告一种简单方法来调节其在不同pH值下的药物释放程度。这是通过使用静电逐层（LbL）自组装方法在负载Dox的锂皂石纳米颗粒表面交替沉积阳离子聚（烯丙胺）盐酸盐和阴离子聚（苯乙烯磺酸钠）（PAH/PSS）聚电解质来实现的。通过动态光散射和zeta电位测量证实了聚电解质多层包覆的Dox/锂皂石系统的成功形成。进行了系统研究以评估它们的药物释放曲线和抗癌效率。我们的结果表明，聚电解质多层的存在改善了锂皂石的缓释特性，并允许在中性和酸性pH值下对药物释放程度进行微调。聚电解质多层包覆的Dox/锂皂石系统对MCF-7细胞呈现的细胞毒性与药物递送曲线一致。此外，细胞摄取研究表明，聚电解质多层包覆的Dox/锂皂石纳米颗粒可被细胞有效内化，导致Dox在细胞核中积累。
