Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, Rome 00133, Italy.
Department of Chemical Science and Technology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, Rome 00133, Italy.
Biomaterials. 2015 Jan;38:22-35. doi: 10.1016/j.biomaterials.2014.10.057. Epub 2014 Nov 9.
Nanodiamond application in biotechnological and medical fields is nowadays in continuous progress. In fact, biocompatibility, reduced dimensions and high surface chemical interaction are specific features that make nanodiamonds perfect intracellular carriers of bioactive compounds. By confocal microscopy, we confirmed that nanodiamonds were able to penetrate in cell cytoplasm but we also demonstrated how they remained embedded in nuclear membrane just exposing some little portions into nuclear area, definitively clarifying this topic. In this work, for the first time, nanodiamonds were conjugated with plant secondary metabolites, ciproten and quercetin. Moreover, since drug-loading on nanoparticles was strongly conditioned by their chemical surface, different types of nanodiamonds (oxidized, wet chemical reduced and plasma reduced) were synthesized in this work and then functionalized with plant compounds. We found that ciproten and quercetin antiproliferative effects, on human (HeLa) and murine (B16F10) tumor cells, were improved after nanodiamond conjugation. Moreover, plant molecules highly reduced their in vitro pro-oxidant, cytotoxic and pro-apoptotic activity when associated with nanodiamond. We are led to suppose that natural drug-nanodiamond adducts would act at cellular level by different molecular mechanisms with respect to plant metabolite pure forms. Finally, our results showed that chemical and structural modifications of nanodiamond surfaces influenced the bioactivity of transported drugs. According to all these evidences, this work can be considered as a promotional research to favor the use of bioactive plant molecules associated with nanodiamonds for therapeutic purposes.
纳米金刚石在生物技术和医学领域的应用如今正在不断发展。事实上,生物相容性、减小的尺寸和高表面化学相互作用是使纳米金刚石成为生物活性化合物的理想细胞内载体的特定特征。通过共聚焦显微镜,我们证实了纳米金刚石能够穿透细胞质,但我们也证明了它们如何仍然嵌入在核膜中,仅将一些小部分暴露在核区域内,明确地澄清了这个问题。在这项工作中,纳米金刚石首次与植物次生代谢物环丙嗪和槲皮素结合。此外,由于纳米粒子上的药物负载强烈取决于其化学表面,因此在这项工作中合成了不同类型的纳米金刚石(氧化、湿化学还原和等离子体还原),然后用植物化合物进行功能化。我们发现,环丙嗪和槲皮素对人(HeLa)和鼠(B16F10)肿瘤细胞的抗增殖作用在与纳米金刚石结合后得到了改善。此外,当与纳米金刚石结合时,植物分子大大降低了其体外的促氧化剂、细胞毒性和促凋亡活性。我们假设天然药物-纳米金刚石加合物将通过不同于植物代谢物纯形式的不同分子机制在细胞水平上发挥作用。最后,我们的结果表明,纳米金刚石表面的化学和结构修饰影响了运输药物的生物活性。根据所有这些证据,这项工作可以被认为是促进使用与纳米金刚石结合的生物活性植物分子用于治疗目的的研究。