Designing Drug-Coated Nanodiamonds for Targeted Delivery

Using nanoparticles has gained attention due to their small size and high surface to volume ratio, but there are many concerns about their harmfulness for the living organisms. According to the studies available in the literature, the NDs are theleast toxic and the most biocompatible carbon nanomaterials and therefore can be considered as a suitable nanocarriers for targeted drug delivery, improving therapeutic value of various drugs [1]. Nanodiamonds (ND) have emerged since about a decade ago as a key platform for many developments in nanoscience and nanotechnology due to their outstanding mechanical performance, biocompatibility and unique properties. Their large accessible surface allows enlarged loading of drugs, while their surface chemistry could be easily tuned to increase permeability into targeted tissue and enhance the selectivity of drug actions while reducing the adverse effects of their use [2]. NDs also interact with plasma proteins in the blood and cellular enzymes upon crossing the target cell membrane. As a result, the nanoformulation is rapidly excreted from the bloodstream by the kidneys, ending up in an incomplete delivery of the drug release at the targeted sites. By using different techniques of drug coating over the nanoparticle, the circulation time of a drugs in blood, their permeability pathways into the target cells, and controlled release inside can be controlled by changing the type of coating, which greatly affects the overall properties of the nanocarrier. Recently, NDs were reported to affect endothelial permeability to deliver anticancer drugs [3, 4]. Another report included delivery of the quaternary oxime antidotes to the cell lines simulating BBB in order to manage acute poisoning with organophosphorus toxic agents [5].<br/>This study focuses on the basic concept underlying the approach for tuning behavior of NPs by covalent bunding on the ND surface <i>vs</i> non-covalently bound agents - (i) pyridinium oximes as scavengers or antidotes-cholinesterase reactivators; (ii) oxazolopyrimidines as promising anticancer agents [6], whereby the fundamental characteristics such as transportation into (i) BBB simulating (MDCK and HUVEC grown in astrocyte medium) and (ii) oncogenic cells (HeLa), localization inside, and anti-cancer activity (cell viability) were studied. The properties of obtained nanocarriers (surface drug density, aggregation, surface modification) were investigated by FTIR, XRD, DLS, and TEM. Shedding light on the way of cell permeability may give a clue for a surface coating to achieve targeted drug delivery. The advantages of different coating techniques are being discussed.<br/>Aknowledgement. DB and YK acknowledges NATO SPS MYP No.G5565 (DEFIR) for support of this study.<br/>References:<br/>[1] K. Turcheniuk, V. N. Mochalin <i>Nanotechnology</i>, 2017, 28, 27.<br/>[2] N. Bondon et al. <i>Journal of Materials Chemistry B</i> 2020, 8 (48), 10878-10896.<br/>[3] M. I. Setyawati, V. N. Mochalin, and D. T Leong. ACS Nano, 2016, 10, 1170.<br/>[4] H. Li, D. Zeng, Z. Wang, L. Fang, F. LI, Z. Wang. Nanomedicine 2018, 13, 981<br/>[5] (a)Y. Karpichev et al. 2020 Virtual MRS Spring Meeting & Exhibit, Boston, 2020. Material Research Society, S.NM01.10.06. (b) D. Bondar et al, submitted.<br/>[6] Ye. Velihina, Th. Scattolin, D. Bondar, S. Pil'o, N. Obernikhina, O. Kachkovskyi, I. Semenyuta, I. Caligiuri, F. Rizzolio, V. Brovarets, Y. Karpichev, S.P. Nolan. <i>Helvetica Chimica Acta</i>, 2020, 103 (12), #e2000169