CONTEXT

Biological optical imaging greatly relies upon the use of sensitive and stable optical labels. So far, organic dyes, quantum dots, and metal nanoparticles are the most commonly used optical labels but still have some limitations. When used in vivo, fluorescent probes present numerous drawbacks such as autofluorescence coming from tissue organic components during probe illumination. In addition, deep tissue imaging is difficult because of critical absorption from major components present in living organism (water, melanin, haemoglobin, lipids).

TECHNICAL DESCRIPTION

The invention relates to using persistent luminescence nanoparticles, functionalized if necessary, in the form of a diagnosis agent for an in vivo optical imaging. Said nanoparticles are preferably consist of a compound selected from a group comprising gallates, aluminates, indates, gallogermanates, galloaluminates, galloindates, gallium oxides, indium oxides, magnesium oxides, wherein said compound is doped with one rare earth ion or with one transition metal ion (chrome, europium, cerium, nickel, iron, copper, cobalt).

These inorganic persistent luminescence particles can be excited in vivo after injection (wavelength between 550-1000 nm) before emitting in near-infrared range.

The nanoparticles can be embedded in mesoporous silica for the delivery of biological products. The invention also relates to using these nanoparticles for an in vivo multimodal optical/MRI imaging through adding paramagnetic elements Cr³⁺, Mn²⁺, Gd³⁺, Fe³⁺ or Ni³⁺.

BENEFITS

This method has important advantages over current imaging methods:

• Long lasting luminescence – nanoparticles excited in situ after injection
• Observation in real time without autofluorescence of endogenous fluorophores
• Possible real-time monitoring of biodistribution of cells
• Functionalization with molecules of biological interest
• Size of the nanoparticles compatible with biological applications (50 to 100 nm)
• Bimodal optical/MRI imaging

INDUSTRIAL APPLICATIONS

This innovation could be used for:

• In vivo imaging
• In vitro diagnosis with pre-functionalized nanoparticles
• Theranostics (by use of mesoporous persistent luminescence “core-shell”)

DEVELOPMENT STAGE

Several developments are currently being explored regarding the present invention:

• In vivo monitoring of labelled cells for preclinical cell therapy research
• In vivo monitoring of orally-administered persistent luminescence nanoparticles
• Real-time monitoring and biodistribution of capsules in the gastro-intestinal tract
• Novel compositions to favor re-excitation in vivo
• Production of ROS induced by persistent luminescence nanoparticles, applications in photodynamic therapy (PDT)
• Interaction of persistent luminescence nanoparticles with model proteins
• Study of their in vivo toxicity

Articles

Maldiney et al., 2014, Nat. Mater. 13(4):418-426

Maldiney et al., 2014, Nanoscale. 6(22):13970-6

Maldiney et al., 2012, Bioconjug. Chem. 23(3):472-478.