Sensitive trimodal MRI-SERRS-fluorescence detection of cancer cells with stable magneto-plasmonic nanoprobes

Abstract : Novel magneto-plasmonic nanoprobes were designed for multimodal diagnosis of cancer by combination of Magnetic Resonance Imaging (MRI), Surface-Enhanced Resonance Raman Scattering (SERRS) and fluorescence emission in the very near infrared (VNIR). A controlled electrostatic assembly of silver nanoparticles (Ag NPs), superparamagnetic iron oxide nanoparticles (SPIONs), VNIR dye Nile blue (NB) and biopolymer chitosan (Chi) was used to formulate the AgIONs-Chi nanoprobes. The formulation protocol did not involve organic solvents, was rapid and efficient as confirmed by magnetic sorting. The SERRS response of the nanoprobes was very intense and constant for days. It decreased linearly upon 1000-fold dilution and was still recognizable at 0.1 nM NB concentration. After 30 days storage, the SERRS loss was less than 30% and the hydrodynamic size of the AgIONs-Chi in PBS remained below 200nm. The gradual decrease of the ratio SERRS/fluorescence allowed monitoring the release of the fluorescent molecule upon long-term nanoprobe dissociation. The AgIONs-Chi exhibited two-fold higher MRI contrast than that of commercially available SPION suspensions. Finally, the nanoprobes were actively uptaken by HeLa cancer cells and ensured trimodal MRI-SERRSfluorescence detection of 10μL cell inclusions in cm-sized agarose gels used here as phantom models of microtumors. The above results show that the magneto-plasmonic AgIONs-Chi are promising substrates for SERRS analysis in solution and for multimodal imaging of cancer cells.