Fluorescent Nanodiamond Applications for Cellular Process Sensing and Cell Tracking.

Sandra Claveau,François Treussart,Jean-Rémi Bertrand

doi:10.3390/mi9050247

Abstract

Diamond nanocrystals smaller than 100 nm (nanodiamonds) are now recognized to be highly biocompatible. They can be made fluorescent with perfect photostability by creating nitrogen-vacancy (NV) color centers in the diamond lattice. The resulting fluorescent nanodiamonds (FND) have been used since the late 2000s as fluorescent probes for short- or long-term analysis. FND can be used both at the subcellular scale and the single cell scale. Their limited sub-diffraction size allows them to track intracellular processes with high spatio-temporal resolution and high contrast from the surrounding environment. FND can also track the fate of therapeutic compounds or whole cells in the organs of an organism. This review presents examples of FND applications (1) for intra and intercellular molecular processes sensing, also introducing the different potential biosensing applications based on the optically detectable electron spin resonance of NV− centers; and (2) for tracking, firstly, FND themselves to determine their biodistribution, and secondly, using FND as cell tracking probes for diagnosis or follow-up purposes in oncology and regenerative medicine.

Highlights

Nanodiamonds (NDs) are diamond phase carbon nanomaterials that were initially used for their strong abrasive properties and as lubricant additives [1] for industrial applications
They are produced on a large scale by different processes [2] that include explosion during the detonation stage [3], the milling of diamond microcrystals synthesized by high-pressure high-temperature process (HPHT), by plasma-assisted chemical vapor deposition (CVD) [4], or by laser ablation [5]
ND can be endowed with remarkable properties, in particular photoluminescence via embedded point defect with perfect photostability, yielding fluorescent NDs (FNDs) [6,7] with optically detectable magnetic resonance (ODMR) properties [8]

Summary

Introduction

Nanodiamonds (NDs) are diamond phase carbon nanomaterials that were initially used for their strong abrasive properties and as lubricant additives [1] for industrial applications. Pristine or functionalized ND have been repeatedly reported to be non-toxic for cells and organisms [10,11,12] Considering this set of unique properties, NDs are considered as a valuable nanoparticle for biomedical applications to study intracellular processes and to follow the fate of molecule delivery when NDs are used as a drug delivery platform. Taking advantage of FND fluorescence, Li et al demonstrated that the grafting of Tf at the surface of FND improved their internalization in HeLa cells [22] They reported that when cell’s Tf receptors were pre-saturated by free Tf, FND uptake decreased, indicating that it is a Tf-receptor-mediated process. Free Dox was more toxic (reduction of cell viability) on normal cells when it is free that when vectorized by FND-Tf, but FND-Tf-Dox was as toxic as free Dox on cancer cells

Sensing Intra- and Inter-Cellular Biological Processes

Labelling Cell Membrane in Culture and Probing Receptor Dynamics

Tracking the Fate of Molecules and Their ND Vector in Organisms