ABSTRACT
We have recently reported the design and use of inorganic nanoparticles with persistent luminescence properties. Such nanoparticles can be excited with a UV lamp for 2min and emit light in the near-infrared area for dozen of minutes without any further excitation. This property is of particular interest for small animal optical imaging, since it avoids the autofluorescence of endogenous fluorophores which is one major problem encountered when using fluorescent probes. We report herein the synthesis of persistent luminescence nanoparticles (PLNPs) and their functionalization with two small targeting molecules: biotin and Rak-2. We provide characterization of each PLNP as well as preliminary evidence of the ability of PLNP-PEG-Biotin to target streptavidin and PLNP-PEG-Rak-2 to bind prostate cancer cells in vitro.
Subject(s)
Chemistry Techniques, Synthetic/methods , Diagnostic Imaging/methods , Drug Delivery Systems/methods , Luminescent Agents/administration & dosage , Nanoparticles/chemistry , Biotin/chemistry , Calcium Chloride/chemistry , Cell Line, Tumor , Chlorides/administration & dosage , Chlorides/chemistry , Drug Stability , Dysprosium/administration & dosage , Dysprosium/chemistry , Europium/administration & dosage , Europium/chemistry , Humans , Luminescent Agents/chemistry , Magnesium Compounds/chemistry , Male , Manganese Compounds/administration & dosage , Manganese Compounds/chemistry , Nitrates/administration & dosage , Nitrates/chemistry , Polyethylene Glycols/chemistry , Prostatic Neoplasms , Protein Binding , Silanes/chemistry , Spectroscopy, Fourier Transform Infrared , Static Electricity , Streptavidin/chemistry , Surface Properties , Thermogravimetry , Zinc Compounds/chemistryABSTRACT
A growing insight toward optical sensors has led to several major improvements in the development of convenient probes for in vivo imaging. Efficient optical detection using quantum dots (QDs) as well as near-infrared organic dyes relies on several key driving principles: the ability to lower background absorption or autofluorescence from tissue, a good photostability of the probe, and a high quantum yield. In this article, we report the real-time biodistribution monitoring of lanthanide-doped persistent luminescence nanoparticles (PLNP), emitting in the near-infrared window, in healthy and tumor-bearing mice. We focused on the influence of hydrodynamic diameter, ranging from 80 to 180 nm, and polyethylene glycol (PEG) surface coating on the behavior of our probes. Tissue distribution was found to be highly dependent on surface coverage as well as core diameter. The amount of PLNP in the blood was highly increased for small (d < 80 nm) and stealth particles. On the opposite, PEG shield molecular weight, ranging from 5 to 20 kDa, had only negligible influence on the in vivo biodistribution of our silicate-based material.
Subject(s)
Luminescent Agents/chemistry , Luminescent Agents/pharmacokinetics , Nanoparticles/chemistry , Particle Size , Polyethylene Glycols/chemistry , Animals , Carcinoma, Lewis Lung/metabolism , Cell Line, Tumor , Female , Mice , Mice, Inbred BALB C , Molecular Imaging , Molecular Weight , Surface PropertiesABSTRACT
Starting from suitably protected amino acids, mercaptoimidazoles were synthesized either from the acid or including the amine nitrogen itself. A preliminary optimisation study led to efficient conditions for the obtention of the imidazole ring. These conditions are compatible with the presence of amino acid or dipeptide scaffolds.
