Unraveling In Vivo Brain Transport of Protein‐Coated Fluorescent Nanodiamonds

Abstract

Nanotheranostics, combining diagnostics and therapy, has the potential to revolutionize treatment of neurological disorders. But one of the major obstacles for treating central nervous system diseases is the blood–brain barrier (BBB) preventing systemic delivery of drugs and optical probes into the brain. To overcome these limitations, nanodiamonds (NDs) are investigated in this study as they are a powerful sensing and imaging platform for various biological applications and possess outstanding stable far‐red fluorescence, do not photobleach, and are highly biocompatible. Herein, fluorescent NDs encapsulated by a customized human serum albumin–based biopolymer (polyethylene glycol) coating (dcHSA‐PEG) are taken up by target brain cells. In vitro BBB models reveal transcytosis and an additional direct cell–cell transport via tunneling nanotubes. Systemic application of dcHSA‐NDs confirms their ability to cross the BBB in a mouse model. Tracking of dcHSA‐NDs is possible at the single cell level and reveals their uptake into neurons and astrocytes in vivo. This study shows for the first time systemic NDs brain delivery and suggests transport mechanisms across the BBB and direct cell–cell transport. Fluorescent NDs are envisioned as traceable transporters for in vivo brain imaging, sensing, and drug delivery.

Application of Carbon Nanoparticles in Oncology and Regenerative Medicine

“…Anionic MWCNTs have the highest transport levels in the in vitro human BBB model compared to non-ionic or cationic nanotubes [26]. This is confirmed by Moscariello et al [45]…”

“…Anionic MWCNTs have the highest transport levels in the in vitro human BBB model compared to non-ionic or cationic nanotubes [26]. This is confirmed by Moscariello et al [45] who showed that fluorescent NDs surrounded by a biopolymer coating based on human serum albumin (dcHSA-PEG) were taken up by target brain cells. The use of dcHSA-ND confirms the ability of complexes/conjugates to cross the BBB in a mouse model.…”

“…This resulted in photoluminescence of the nanotubes in the infrared range. This method allowed to distinguish between normal and cancer cells [ 44 , 45 , 46 , 47 ]. The specific binding of antibodies-labelled nanotubes to antigens of cancer cells is shown in Scheme 1 .…”

“…Observation of dcHSA-ND is possible at the single cell level and reveals its in vivo uptake into neurons and astrocytes. This study shows NDs penetration into the brain via a BBB transport mechanism [ 45 ].…”

Biopolymer‐Based Coatings: Promising Strategies to Improve the Biocompatibility and Functionality of Materials Used in Biomedical Engineering

“…A third research area, where biopolymer‐based coatings have emerged as a powerful tool is the field of drug delivery. Here, stealth coatings, [ 143 ] coatings for (cell) specific targeting [ 144 ] or coatings as drug depots [ 145 ] have applications in nanomedicine, but also macroscopic pharmaceutical objects such as dragées [ 146 ] benefit from a coating. Moreover, drug‐loaded implant coatings have gained increasing interest; their function is to deal with exogenous pathogens, which enter the surgical site during an implantation operation.…”