Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer's disease.

BACKGROUND: Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery. RESULTS: We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long ß-sheet breaker peptide that is able to recognize amyloid ß (Aß) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains. CONCLUSIONS: The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aß aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aß aggregates involved in the pathogenesis of the Alzheimer disease.

Skull Base Meningiomas and Cranial Nerves Contrast Using Sodium Fluorescein: A New Application of an Old Tool.

Objective The identification of cranial nerves is one of the most challenging goals in the dissection of skull base meningiomas. The authors present an application of sodium fluorescein (SF) in skull base meningiomas with the purpose of improving the identification of cranial nerves. Design A prospective study within-subjects design. Setting Hospital Ernesto Dornelles, Porto Alegre, Brazil. Participants Patients with skull base meningiomas. Main Outcomes Measures Cranial nerve identification. Results The group of nine meningiomas was composed of one cavernous sinus, three petroclival, one tuberculum sellae, two sphenoid wing, one olfactory groove, and one temporal floor meningioma. The SF enhancement in all tumors was strong, and the contrast with cranial nerves clearly evident. There were one definite olfactory nerve deficit, one transient abducens deficit, and one definite hemiparesis. All lesions were resected (Simpson grades 1 and 2). The analysis of the difference of the delta SF wavelength between the meningiomas and cranial nerve contrast was performed by the Wilcoxon signed rank test and showed p = 0.011. Conclusions The contrast between the enhanced meningiomas and cranial nerves was evident and assisted in the visualization and microsurgical dissection of these structures. The anatomical preservation of these structures was improved using the contrast.