Lerra Luigi, Farfalla Annafranca, Sanz Beatriz, Cirillo Giuseppe, Vittorio Orazio, Voli Florida, Le Grand Marion, Curcio Manuela, Nicoletta Fiore Pasquale, Dubrovska Anna, Hampel Silke, Iemma Francesca, Goya Gerardo F
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, NSW 2031, Australia.
Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende (CS), Italy.
Pharmaceutics. 2018 Dec 22;11(1):3. doi: 10.3390/pharmaceutics11010003.
With the aim to obtain a site-specific doxorubicin (DOX) delivery in neuroblastoma SH-SY5Y cells, we designed an hybrid nanocarrier combining graphene oxide (GO) and magnetic iron oxide nanoparticles (MNPs), acting as core elements, and a curcumin⁻human serum albumin conjugate as functional coating. The nanohybrid, synthesized by redox reaction between the MNPs@GO system and albumin bioconjugate, consisted of MNPs@GO nanosheets homogeneously coated by the bioconjugate as verified by SEM investigations. Drug release experiments showed a pH-responsive behavior with higher release amounts in acidic (45% at pH 5.0) vs. neutral (28% at pH 7.4) environments. Cell internalization studies proved the presence of nanohybrid inside SH-SY5Y cytoplasm. The improved efficacy obtained in viability assays is given by the synergy of functional coating and MNPs constituting the nanohybrids: while curcumin moieties were able to keep low DOX cytotoxicity levels (at concentrations of 0.44⁻0.88 µM), the presence of MNPs allowed remote actuation on the nanohybrid by a magnetic field, increasing the dose delivered at the target site.
为了实现神经母细胞瘤SH-SY5Y细胞中阿霉素(DOX)的位点特异性递送,我们设计了一种混合纳米载体,其核心元素为氧化石墨烯(GO)和磁性氧化铁纳米颗粒(MNPs),功能涂层为姜黄素-人血清白蛋白缀合物。通过MNPs@GO体系与白蛋白生物缀合物之间的氧化还原反应合成的纳米杂化物,由生物缀合物均匀包覆的MNPs@GO纳米片组成,扫描电子显微镜(SEM)研究证实了这一点。药物释放实验表明,该纳米杂化物具有pH响应行为,在酸性环境(pH 5.0时释放量为45%)中的释放量高于中性环境(pH 7.4时释放量为28%)。细胞内化研究证明纳米杂化物存在于SH-SY5Y细胞质中。在活力测定中获得的疗效改善归因于构成纳米杂化物的功能涂层和MNPs的协同作用:虽然姜黄素部分能够保持较低的DOX细胞毒性水平(浓度为0.44-0.88 µM),但MNPs 的存在允许通过磁场对纳米杂化物进行远程驱动,增加在靶位点递送的剂量。