A Dual‐Modal SERS/Fluorescence Gold Nanoparticle Probe for Mitochondrial Imaging

Abstract

A novel SERS/fluorescent multimodal imaging probe for mitochondria has been synthesised using 12 nm diameter gold nanoparticles (AuNP) surface functionalised with a rhodamine thiol derivative ligand. The normal pH‐dependent fluorescence of the rhodamine‐based ligand is inversed when it is conjugated with the AuNP and higher emission intensity is observed at basic pH. This switch correlates to a pKa at pH 6.62, which makes it an ideal candidate for a pH‐sensitive imaging probe in the biological range (pH 6.5–7.4). The observed pH sensitivity of the ligand when attached to the AuNP is thought to be due to the formation of a spirolactam ring, going from positively charged (+18 mV) to negatively charged (−60 mV) as the pH is changed from acidic to basic. Additionally, conjugation of the ligand to the AuNP serves to enhance the Raman signal of the rhodamine ligand through surface‐enhanced Raman scattering (SERS). Confocal microscopy has shown that the probe enters HEK293 (kidney), A2780 (ovarian cancer) and Min6 (pancreatic beta) cells within an hour and a half incubation time. The probe was shown to localise in the mitochondria, thus providing a novel pH‐dependent SERS/fluorescent multimodal imaging probe for mitochondria.

Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units

“…Superparamagnetic iron oxide nanoparticles (SPIONs) such as Feridex/Endorem and Resovist have been approved for clinical use while other nanoparticle‐based formulations are undergoing clinical trials . Gold nanoparticles (GNPs) are amongst the most studied due to their biocompatibility, the ease with which their dimensions can be controlled and the well‐established methods for attachment of surface units through sulfur linkages (principally thiols) . The thermal response to near‐IR light irradiation of gold nanostructures (photothermal therapy, PTT) has also attracted interest, but it is less established than the more widely used photodynamic therapy (PDT), where cytotoxic singlet oxygen/radicals are generated by the photoexcitation of photosensitizers administered to the patient .…”

“…[6] Gold nanoparticles (GNPs) are amongst the most studied duet ot heir biocompatibility,t he ease with which their dimensions can be controlled and the well-established methodsf or attachment of surface units through sulfur linkages (principally thiols). [7] The thermal re-sponse to near-IR light irradiation of gold nanostructures (photothermal therapy,P TT) has also attracted interest, buti ti sl ess established than the more widely used photodynamic therapy (PDT),w here cytotoxic singlet oxygen/radicals are generated by the photoexcitation of photosensitizers administered to the patient. [8] The accumulation of gold nanoparticles at tumour sites due to their leaky,i mmature vasculature with wider fenestrations than normal mature blood vessels,k nown as the enhancedp ermeability and retention (EPR) effect, [9] has led to the increasing use of GNPs in cancer therapy research.…”

Gold nanomaterials functionalised with gadolinium chelates and their application in multimodal imaging and therapy

“…74 A 'smart' rhodamine-based dye, which emits fluorescence of variable intensity depending on local pH, has also been tethered to gold nanoparticles for use in cancer imaging. 75 Interestingly, the sensitivity of the dye to changes in pH conditions was found to increase on binding to the gold nanoparticle surface, possibly due to the large variation in surface charge experienced by the gold nanoparticles at pH values between 5.2 and 7.8. 75 Gold nanoparticles have also been used as a platform to combine MRI and single photon emission computed tomography (SPECT) imaging agents.…”

“…75 Interestingly, the sensitivity of the dye to changes in pH conditions was found to increase on binding to the gold nanoparticle surface, possibly due to the large variation in surface charge experienced by the gold nanoparticles at pH values between 5.2 and 7.8. 75 Gold nanoparticles have also been used as a platform to combine MRI and single photon emission computed tomography (SPECT) imaging agents. DOTA-based chelators designed to encapsulate Gd 3+ ions can also be used to achieve the complexation of 67 Ga 3+ ions.…”

SERS Quantification and Characterization of Proteins and Other Biomolecules

“…Thus, the parameters, such as wavelength and power of laser and spectral acquisition time, play important roles in Raman images. Therefore, the strategies based on fluorescence combining with SERS can improve the time and reduce the sample exposure to the laser. − This alternative allows for the fast localization of the area of interest with fluorescence and then a deeper study of that area with SERS. In general, SEPs are poised to have a large impact on cellular imaging, including in immunohistochemistry, due to their narrow and complex spectral features.…”