MCNANO · “Multi-component nanoparticles as bimodal contrast agents for MRI and optical detection of tumors and for targeted photodynamic therapy”
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-04-01 → 2018-03-31
- EU contribution
- €172,800
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
“Multi-component nanoparticles as bimodal contrast agents for MRI and optical detection of tumors and for targeted photodynamic therapy”
Magnetic resonance imaging (MRI) is a powerful technique for obtaining tomographic images of biological targets in a noninvasive manner, with high spatial/temporal resolution, which makes it a vital component for diagnosing diseases such as cancer. Numerous studies have shown that the diagnostic value of MRI can be further improved by applying vectorized contrast agents, capable of delivering a high payload of para magnetic/superparamagnetic substances at the site of interest. However, because of the low intrinsic sensitivity of MRI compared to optical imaging, a relatively large local concentration of contrast agent is required to achieve the desired contrast enhancement. Looking exclusively at the sensitivity, optical imaging (OI) is more adequate for imaging as the local concentrations of contrast agents required are significantly lower. This issue of higher injection dose can be circumvented by adopting the technique of multimodal imaging, where different imaging modalities are combined within the frame of a single examination to obtain complementary information. Thus in the present study, a novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent was developed, based on core–shell lanthanide fluoride nanoparticles composed of a b-NaHoF4 core plus a b-NaGdF4:Yb3+, Tm 3+ shell with an average size of ~24 nm. The biocompatibility of the particles was ensured by a surface modification with poly acrylic acid (PAA) and further functionalization with an affinity ligand, folic acid (FA). When excited using 980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense emission at 802 nm with lifetime of 791+/_3 ms, due to the transition 3H4!3H6 of Tm3+. Proton nuclear magnetic relaxation dispersion (1H-NMRD) studies and magnetic resonance (MR) phantom imaging showed that the newly synthesized nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface (NP-PAA-FA), can act mainly as a T1weighted contrast agent below 1.5 T, a T1/T2 dual-weighted contrast agent at 3 T, and as highly efficient T2-weighted contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low cytotoxicity and no detectable cellular damage up to a dose of 500 mgmL-1.
Data: CORDIS, © European Union
Project objective
The main aim of this proposal is to synthesize a range of lanthanide containing nanoparticles with an upconverting core, that can be excited in the infrared region to yield emission in the visible range, as for MRI and optical imaging. The nanoparticles will be covered with a rare earth doped MRI active shell and decorated with targeting moieties, which offers a means of targeting cancer cells that greatly over express the receptors. Further we will develop “phototheranostic” agents by anchoring the photo active anti cancer drug in between the receptors and the surface of upconverting/MRI active nanoparticle. A platform for synthesis of water soluble, modular target specific bimodal agents based on nanoprobes will be developed that will exhibit efficient upconverted photoluminescence from the rare-earth ions (Er3+/Tm3+) doped into fluoride nanomatrix. Simultaneously, the Tb3+/Dy3+/Ho3+ present at the shell will make them suitable as T2 contrast agents for MRI. Specific tumor targeting strategies will be developed by attaching targeting components like folic acid, cholesterol or cyclic-RGD to the surface of the nanoparticles. Functionalization of nanoparticles with [Pt(N3)2(OH)2(NH2-R)(py)] drug, which can be photoactivated by the blue light emitted from the nanoparticle core upon excitation at 980, will result in a novel phototheranostic anti-cancer agent. This system may allow a large degree of control of the therapeutic efficacy and ultimately lead to simultaneous diagnosis and treatment in clinical applications. The unique multidisciplinary approach adopted here which combines areas of nano-chemistry, spectroscopy and bio-imaging, is expected to lead to a disruptive change in the area of cancer research. The combination of these areas would allow for the first time the development of biocompatible “phototheranostic” agents for the simultaneous detection by MRI/optical imaging and cure of the cancer- affected tissues.
Original text from CORDIS.
Participants
- KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenCoordinatorBelgium
Links
Data: CORDIS, © European Union