Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions

Abstract

With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable properties have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made towards the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed.

Adoption of nanodiamonds as biomedical materials for bone repair

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Keywords: gene/drug delivery • nanodiamonds • therapeutics Nanodiamonds (NDs) are an emerging class of biologically compatible carbon-based nanomaterials that possess a set of unique properties essential for the design of innovative therapies in the fields of drug delivery, tissue engineering and bioimaging [1]. For instance, the high surface area along with the tunable surface chemistry enables the physical adsorption or covalent conjugation of a variety of therapeutic molecules, such as drugs, peptides and growth factors [2][3][4][5].

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Chemical Functionalization of Nanodiamonds: Opportunities and Challenges Ahead

“…[12] Siloxane functionalization can be used to enhance the surface area of the nanoparticles and thereby the drug-loading capacity of the materials.T his approach has been successfully used to covalently anchor dyes and receptors onto silica-grafted NDs via click chemistry,with interesting in-vitro results. [3] Thed escribed functionalization reactions are aimed for the application of NDs in the biomedical field. However, there are also many other possibilities that allow to modify the NDs with different functional groups.F or example, hydroxylated NDs can react with alkyl chlorides (Williamson reaction), while hydrogenated NDs can be easily functionalized with alkenes after UV activation or with diazonium salts (Tour reaction).…”

“…Additionally,t he ND surface can exhibit an unexpected reactivity compared to usual molecules.F or instance,f luorinated NDs (prepared via fluorine plasma) can easily react with amines and Grignard reagents. [3,23] Furthermore,c arboxylic groups present on the ND surface can be easily converted into azido groups,obtaining amaterial readily feasible for click chemistry. [28] Fort hese reasons,w e believe that there is still room for improving functionalization strategies for final applications.…”

“…However,c oronation and aggregation can be modulated via surface functionalization. [3] In the case of in-vivo fluorescence imaging,the number of luminescent centers in single NDs are very limited, leading to insufficient emission intensities that hardly penetrate skin and tissues.Additionally,tocreate N-V centers in NDs,i rradiation by high-energy electron/heliumion beams and subsequent high-temperature annealing are required, which largely increase the cost of fluorescent NDs and inevitably destroy the intrinsic surface functionality. Finally,increasing the colloidal stability of fluorescent NDs to meet the requirements of in-vivo studies still remains challenging.F or these reasons,d ifferent groups are developing strategies to prepare highly doped NDs already during synthesis.…”

“…Nowadays,n anotechnology is widening its field of application while being more and more integrated into our daily life.T he preparation of pure,h omogeneous,a nd monodisperse nano-objects is highly desirable.I nt his context, nanodiamonds (NDs) have been extensively studied, and they find many cutting-edge applications in several domains. [1][2][3] NDs constitute af amily of nanomaterials that has ac ore with acommon sp 3 carbon structure,but avariety of sizes,shapes, and surface chemistry.Bydifferent synthetic approaches,itis possible to obtain very small particles of 3t o4nm size or homogeneous films with micron-size thickness.T he preparation methods also influence the quality,quantity,and surface chemistry of the final material. Them ost popular synthetic strategies for the production of NDs comprise detonation (D-NDs), high pressure/high temperature (HPHT-NDs), and chemical vapor deposition (CVD-NDs).…”