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Metallated doped conjugated polymer nanoparticles as bimodal imaging agent for cancer detection: application in a preclinical glioblastoma model

AuthorsIbarra, Luis E.; Arias-Ramos, Nuria; Guillén Gómez, M. J.; Morales, G.; Chesta, Carlos A.; Rivarola, Viviana A.; López-Larrubia, Pilar ; Palacios, Rodrigo E.
Issue Date3-Oct-2019
Citation37th Annual Meeting of European Society for Magnetic Resonance In Medicine and Biology (ESMRMB) (2019)
Abstract[Purpose/Introduction]: The possibility of bringing together several functions into a single nanostructure offers great potential in theranostic nanomedicine. Fluorescence and magnetic resonance dualmodal imaging nanoprobes are highly desired materials in molecular imaging, but also have potential use in clinical diagnosis with high precision and accuracy. Conjugated polymer nanoparticles (CPNs) possess many useful properties including high brightness, excellent photostability, good water-dispersibility, low cytotoxicity, and easy synthesis and functionalization, showing promising application in bioimaging and photo-assisted anticancer therapy1-3. Through the incorporation of an appropriate metal core into CPNs, its application as a T1/T2-enhanced magnetic resonance contrast agent could be possible.
[Subjects and Methods]: Our purpose was to develop, characterize and evaluate in vivo CPNs doped with iron oxide, cobalt nanoparticles or metallated porphyrin as potential dual-imaging contrast agents in tumor bearing mice. CPNs were synthetized as we described previously. Iron oxide nanoparticles (IONp)4, cobalt TurboBeadsTM Vinyl (CoTB) or octaethylporphyrin (PtoEH) were used as dopants to incorporate into CPNs synthesis. A fully characterization was perform: DLS, AFM, TEM, and relaxation times measurements for T1 and T2 in MRI applications. Glioma in vivo model was developed injecting C6 cells in the flank of NOD SCID mice. Tumor growth was followed by T2 W MRI in a 7 T system and when tumors reached an appropriated size, CPNs were injected intravenously (IV) or intratumorally (IT) at doses of 0.25 mg/ kg or 0.1 mg/kg respectively. The biodistribution and arrival of CPNs to the tumor tissue were evaluated by MRI and fluorescence in vivo imaging system at different time points.
[Results]: All the doped CPNs had narrow size diameter about 50 – 100 nm and showed good colloidal stability after several months. IONp doped CPNs induced a shortening of T2 relaxation time of water and also were visible by IVIS imaging, so, were selected to continue with MRI and IVIS fluorescence assays (Table 1).In tumor bearing mice, CPNs biodistribution could be followed by in vivo MRI and fluorescence imaging with an increased accumulation in tumors over time allowing dual-modal detection of tumors in a living body (Fig. 1).
[Discussion/Conclusion]: Our results, incorporating fluorophore and metal complex or other functional unit into one CPNs, provide apotential design strategy to fabricate dual/multi-modality theranostic agents for in vitro and in vivo applications in future.
DescriptionTrabajo presentado en el 37th Annual Meeting; European Society for Magnetic Resonance In Medicine and Biology (ESMRMB), celebrado en Rotterdam (Países Bajos) del 3 al 5 de octubre de 2019.
Appears in Collections:(IIBM) Comunicaciones congresos
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