Visualization of Sentinel Lymph Nodes with Mannosylated Fluorescent Nanodiamonds

Abstract

The present study focuses on the development of a sensitive and specific approach for the visualization of sentinel lymph nodes draining the tumor using ultrabright 200‐nm fluorescent nanodiamonds (FNDs) equipped with a designed targeting surface architecture. The FNDs with a narrow size distribution are isolated by differential centrifugation, colloidally stabilized with alkyne‐functionalized poly(glycerol) and modified with a polyvalent array of mannose (FND‐p‐Man). In vitro experiments demonstrate an outstanding increase of the particle internalization by the mannose receptor CD206 (MR) and no significant toxicity. MR involvement is confirmed by blocking ligand binding with mannan and a 15.2 mAb (specific anti‐MR) in J774A.1 mouse macrophage cell line. In vivo mouse experiments confirm increased retention of FND‐p‐Man in sentinel lymph nodes of both healthy and B16 melanoma bearing animals. These results suggest that FND‐p‐Man has potential as a tracer for lymph node visualization in locoregional perioperative cancer diagnostics and as a tool for endoscopic/robotic fluorescence‐guided surgery.

Nanodiamond–Quantum Sensors Reveal Temperature Variation Associated to Hippocampal Neurons Firing

“…Monodisperse ND Preparation: NDs were supplied by Microdiamant Switzerland (MSY 0-0.25, containing ≈100-200 ppm of natural nitrogen impurities) and treated as described previously. [55] Briefly, the NDs were oxidized by air oxygen at 510 °C for 5 h and then wet oxidized in a HF:HNO 3 2:1 v/v stirred mixture at 160 °C for 2 days in a PTFE container. The acids were removed using consecutive centrifugation/washing and the resulting pure oxidized NDs were lyophilized.…”

Evaluation of Cytotoxicity and Bioimaging of Nitrogen-Vacancy Nanodiamonds

“…NV NDs are nanoparticles that carry some intrinsic absorbance/fluorescence properties, resulting from the high-energy synthesis of NDs [ 1 , 2 , 9 , 14 ]. This fluorescence property, along with other physicochemical properties, means that the NV NDs are a highly promising cell-labelling probe for bioimaging [ 8 , 21 , 22 , 23 , 24 ]. We investigate here the characterisation of NDs and their size impact on cytotoxicity, uptake by MSCs, and fluorescence imaging.…”

“…In addition, 200 nm fluorescent NDs were functionalised with poly(glycerol) and mannose for increased retention in sentinel lymph nodes. The in vivo visualization of the lymph nodes demonstrated the potential for cancer diagnostics and guided surgery [ 22 ]. Milled NDs, with a mean particle size of 46 nm, have also shown good uptake in HeLa cells, where the uptake mechanism was most likely clathrin-mediated endocytosis [ 23 ].…”

Nanodiamonds for Biomedical Applications – Features of Interaction with Blood Components and Behavior in the Circulatory System [Review]

“…ND surface functionalization [49][50][51] and coating [52,53] with macromolecules by adsorption or conjugation can affect the ND in vivo safety [54,55], as well as distribution and predominant localization in organism. Thus, in the sentinel lymph nodes of both healthy mice and mice with B16 melanoma, an increased accumulation of fluorescent ND stabilized by alkynefunctionalized polyglycerol and modified by the surface with a polyvalent set of mannoses was observed [56].…”