Multimodal Contrast Agent Enabling pH Sensing Based on Organically Functionalized Gold Nanoshells with Mn-Zn Ferrite Cores

Abstract

Highly complex nanoparticles combining multimodal imaging with the sensing of physical properties in biological systems can considerably enhance biomedical research, but reports demonstrating the performance of a single nanosized probe in several imaging modalities and its sensing potential at the same time are rather scarce. Gold nanoshells with magnetic cores and complex organic functionalization may offer an efficient multimodal platform for magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and fluorescence techniques combined with pH sensing by means of surface-enhanced Raman spectroscopy (SERS). In the present study, the synthesis of gold nanoshells with Mn-Zn ferrite cores is described, and their structure, composition, and fundamental properties are analyzed by powder X-ray diffraction, X-ray fluorescence spectroscopy, transmission electron microscopy, magnetic measurements, and UV-Vis spectroscopy. The gold surface is functionalized with four different model molecules, namely thioglycerol, meso-2,3-dimercaptosuccinate, 11-mercaptoundecanoate, and (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide, to analyze the effect of varying charge and surface chemistry on cells in vitro. After characterization by dynamic and electrophoretic light scattering measurements, it is found that the particles do not exhibit significant cytotoxic effects, irrespective of the surface functionalization. Finally, the gold nanoshells are functionalized with a combination of 4-mercaptobenzoic acid and 7-mercapto-4-methylcoumarin, which introduces a SERS active pH sensor and a covalently attached fluorescent tag at the same time. 1H NMR relaxometry, fluorescence spectroscopy, and PAI demonstrate the multimodal potential of the suggested probe, including extraordinarily high transverse relaxivity, while the SERS study evidences a pH-dependent spectral response.

Dual-Target Multifunctional Superparamagnetic Cationic Nanoliposomes for Multimodal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy of Retinoblastoma

“…Secondly, PFH, ICG and SPIONs were used as multifunctional components of FCNPIFEs to simultaneously realize the functions of imaging /treatment or imaging/targeting, simplifying the synthesis process to some extent and reducing the synthesis cost compared with the other such theranostics nanoparticles. 51 , 52 Thirdly, ICG could display remarkable photothermal and photodynamic effects under the same laser excitation. Though the PDT efficacy of ICG was limited by hypoxia in tumors due to the high oxygen dependency, PFH in FCNPIFEs showed outstanding oxygen reserve capacity and effectively alleviated intratumor hypoxia.…”

Antitumor Applications of Photothermal Agents and Photothermal Synergistic Therapies

“…Because precious metal materials have the advantages of easy surface modification and good biological stability, these factors can improve the PCE [ 61 ]. Currently, the gold nanostructures studied include gold nanorods [ 62 ], gold nanoshells [ 63 ], gold cages, gold nanorings [ 64 ], gold nanoparticles [ 65 ], rice vesicles, and chiral gold nanoparticles [ 66 ]. Since PTT containing gold nanoparticles was first reported in 2003, the research on gold nanomaterials has attracted extensive attention [ 67 ].…”

Gold nanoshells with magnetic cores and a urea-based receptor for SERS sensing of fluoride anions: experimental and computational study

“…This is promising for novel contrast agents with extended applicability for the sensing of local physiological properties or the detection of certain analytes. 11 Previous studies combining principles of molecular recognition with SERS substrates focused mostly on receptors based on biomolecules, like antibodies, and synthetic aptamers, i.e., short single-stranded nucleic acids capable of binding diverse analytes. 16,17 The transduction of the binding event to the SERS signal was almost exclusively achieved either by controlling the distance between a reporter moiety and the SERS substrate (e.g., the binding of an analyte induced a conformational change of the receptor) or by the aggregation of plasmonic nanostructures induced by the analyte.…”

“…This extends their functionality by visualization in magnetic imaging techniques or magnetically assisted separation. In medical applications, they can serve as multimodal contrast agents, 11,12 theranostic tools 12–14 or components of complex biosensors. 15 The magnetic core ensures a contrast effect in magnetic resonance imaging (MRI) or a signal in magnetic particle imaging (MPI), whereas the golden part of the nanoshell can be employed for photoacoustic or SERS imaging.…”

“…This is promising for novel contrast agents with extended applicability for the sensing of local physiological properties or the detection of certain analytes. 11…”