Abstract
The low photostability of conventional organic dyes and the toxicity of cadmium-based luminescent quantum dots have prompted the development of novel probes for in vitro and in vivo labelling. Here, a new fluorescent lanthanide probe based on silica nanoparticles is fabricated and investigated for optically traceable in vitro translocator protein (TSPO) targeting. The targeting and detection of TSPO receptor, overexpressed in several pathological states, including neurodegenerative diseases and cancers, may provide valuable information for the early diagnosis and therapy of human disorders. Green fluorescent terbium(III)-calix[4]arene derivative complexes are encapsulated within silica nanoparticles and surface functionalized amine groups are conjugated with selective TSPO ligands based on a 2-phenylimidazo[1,2-a]pyridine acetamide structure containing derivatizable carboxylic groups. The photophysical properties of the terbium complex, promising for biological labelling, are demonstrated to be successfully conveyed to the realized nanoarchitectures. In addition, the high degree of biocompatibility, assessed by cell viability assay and the selectivity towards TSPO mitochondrial membrane receptors, proven by subcellular fractional studies, highlight targeting potential of this nanostructure for in vitro labelling of mitochondria.
Highlights
Organic [1,2,3,4,5] and organic/inorganic hybrid [6,7,8,9,10,11,12,13,14,15,16] nanoplatforms have been recently developed for biomedical applications, and have demonstrated to be able to play multiple functions that span from investigation of biological process, to imaging and drug delivery
No statistically significant difference has been observed between the PL intensity values of lysosomal and soluble fraction for the not targeted SN22 and SN46 samples. These results demonstrate that the Translocator protein kDa (TSPO) ligands anchored to silica nanoparticles (SNs) surface are able to recognize to a significant extent the specific mitochondrial membrane receptor, providing luminescent silica-based nanostructures that can be delivered and revealed, at subcellular level, in the mitochondria
Two different samples of cadmium free SNs encapsulating lanthanide fluorescent probe based on TbIII ions complex with p-sulfonatothicalix[4]arene (TCAS) ligand have been synthesized and conjugated with the synthetic TSPO ligand
Summary
Organic [1,2,3,4,5] and organic/inorganic hybrid [6,7,8,9,10,11,12,13,14,15,16] nanoplatforms have been recently developed for biomedical applications, and have demonstrated to be able to play multiple functions that span from investigation of biological process, to imaging and drug delivery. Together with shape, porosity for mesoporous silica-based nanostructures and in general surface area, affect the degradation rate of the SNs being faster for smaller NPs rather than larger ones and slower for nonporous nanostructures compared to mesoporous ones [24,25,26,27]
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