Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil.
Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil; Department of Material Science, Federal University of Technology - Paraná, Estr. dos Pioneiros, 3131, CEP 86036-370, Jardim Morumbi, Londrina, Paraná, Brazil; Department of Chemistry, Federal University of Piauí, Campus Petronio Portella, Ininga, Teresina CEP 64049-550, Piauí, Brazil.
Mater Sci Eng C Mater Biol Appl. 2020 Jul;112:110853. doi: 10.1016/j.msec.2020.110853. Epub 2020 Mar 14.
Colorectal cancer (CRC) has a high incidence and resistance to conventional treatments. Curcumin (CUR) is a promising natural product in the treatment of CRC with excellent in vitro results. However, its low bioavailability is a limiting factor in clinical applications. To overcome, CUR was incorporated into hydrogels constituted by chitosan (CHT) and chondroitin sulfate (CS), natural biopolymers, capable of controlled release. Hydrogels were synthesized in ionic liquids (ILs, [Hmim][HSO]) improving the solubility of CHT and the hydrogel properties. Furthermore, CUR was combined with silver nanoparticles (AgNPs) and visible light by Photodynamic Therapy (PDT), which, through the MEO effect (Metal-Enhanced Singlet Oxygen), leads to cell death. It is highlighted the green synthesis of AgNPs using an ultrasound bath. The CHT/CS hydrogels loaded with CUR/AgNPs were properly characterized. Cellular assays showed that the hydrogels (CHT/CS) were not cytotoxic to healthy tissues. However, PDT selective illumination led to inhibition of Caco-2 human colon cancer cells by the CHT/CS/CUR-AgNPs (CC = 91.5 μg mL of hydrogel). The cellular uptake assays showed, in addition to the therapeutic action, that the CUR can works as a diagnostic fluorescence probe (theranostic system). Finally, we highlight our commitment to work with reagents, solvents, and methodologies aiming at the principles of green chemistry.
结直肠癌(CRC)发病率高,对传统治疗方法有耐药性。姜黄素(CUR)是一种很有前途的天然产物,在治疗 CRC 方面具有出色的体外效果。然而,其生物利用度低是其在临床应用中的一个限制因素。为了克服这一问题,CUR 被纳入壳聚糖(CHT)和硫酸软骨素(CS)组成的水凝胶中,这两种天然生物聚合物能够实现药物的控制释放。水凝胶是在离子液体(ILs,[Hmim][HSO])中合成的,这提高了 CHT 的溶解度和水凝胶的性能。此外,CUR 与银纳米粒子(AgNPs)结合,并通过光动力疗法(PDT)与可见光结合,通过 MEO 效应(金属增强单线态氧)导致细胞死亡。值得注意的是,AgNPs 是通过超声浴进行绿色合成的。载有 CUR/AgNPs 的 CHT/CS 水凝胶得到了适当的表征。细胞实验表明,水凝胶(CHT/CS)对健康组织没有细胞毒性。然而,PDT 选择性光照导致 Caco-2 人结肠癌细胞被 CHT/CS/CUR-AgNPs(CC = 91.5μg mL 的水凝胶)抑制。细胞摄取实验表明,除了治疗作用外,CUR 还可以作为诊断荧光探针(治疗诊断系统)。最后,我们强调我们致力于使用试剂、溶剂和方法,以绿色化学的原则为指导。