Nanodiamonds coupled with plant bioactive metabolites: A nanotech approach for cancer therapy

• Published in: Biomaterials Vol. 38; pp. 22 - 35
• Main Authors: Gismondi, Angelo, Reina, Giacomo, Orlanducci, Silvia, Mizzoni, Francesca, Gay, Stefano, Terranova, Maria L, Canini, Antonella
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-2015
• Subjects: Advanced Basic Science; Animals; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic properties; Antiproliferatives; Apoptosis - drug effects; Biocompatibility; Cell Survival - drug effects; Cellular; Ciproten (5,7-dimethoxycoumarin); Conjugation; Coumarins - administration & dosage; Coumarins - chemistry; Dentistry; Diffusion; Drug Carriers - administration & dosage; HeLa Cells; Humans; Materials Testing; Medical; Metabolites; Mice; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanocapsules - ultrastructure; Nanocomposites - administration & dosage; Nanocomposites - chemistry; Nanocomposites - ultrastructure; Nanodiamonds; Nanodiamonds - administration & dosage; Nanodiamonds - chemistry; Nanodiamonds - ultrastructure; Nanostructure; Natural bioactive compounds; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Particle Size; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plants (organisms); Quercetin (3,3′,4′,5,6-pentahydroxyflavone); Quercetin - administration & dosage; Quercetin - chemistry; Surface Properties; Therapeutic approach; Treatment Outcome; Antineoplastic properties; Nanodiamonds; Ciproten (5,7-dimethoxycoumarin); Quercetin (3,3′,4′,5,6-pentahydroxyflavone); Therapeutic approach; Natural bioactive compounds
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.10.057

Abstract 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.