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Red fluorescent AuNDs with conjugation of cholera toxin subunit B (CTB) for extended-distance retro-nerve transporting and long-time neural tracing.

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A retrograde transportation nerve probe, Au nanodots-cholera toxin B subunit (AuNDs-CTB), are prepared and fully characterized, which emit bright red fluorescence and show high quantum yield (7.2%) and good stability.… Click to show full abstract

A retrograde transportation nerve probe, Au nanodots-cholera toxin B subunit (AuNDs-CTB), are prepared and fully characterized, which emit bright red fluorescence and show high quantum yield (7.2%) and good stability. The fluorescence emitted by the AuNDs is constant across a wide pH range (4-10) and after prolonged UV irradiation (>4 h). Previously, CTB has shown targeting characteristic for nerve cells with high sensitivity and effectiveness. After linking CTB to AuNDs through amidation reactions, AuNDs-CTB are obtained with excellent fluorescence property, nerve target characteristic, and, particularly, neural retrograde transportation feature. The red emission of the AuNDs-CTB is well distinguished from the blue autofluorescence of normal tissues, which provides potential for detection by naked eyes. Further, the fluorescence emission intensity maintains for 10 days in vivo, suggesting great utility for long-time monitoring and sensing of the nerve tissue. Furthermore, the AuNDs-CTB with bright red fluorescence can travel through the peripheral nerve to the spinal cord rapidly by retrograde transportation. The transportation occurs for a long distance (>5 cm) within only 2 days after injection of the AuNDs-CTB into the sciatic nerve. The present study exhibits a novel method for nerve visualization and drug delivery. Statement of significance Au nanodots (AuNDs) conjugated with cholera toxin subunit B (CTB) have been developed for nerve labeling and neural retro-transporting. The red fluorescence from AuNDs-CTB is stable in vitro (pH 4-10 and 4 h UV irradiation) and in vivo (for a long time, more than 10 days). When injecting AuNDs-CTB into the sciatic nerve located at the midpiece of the thigh, the targeted nerve emits bright red fluorescence under UV light. Furthermore, the nerve can retrograde transport the AuNDs-CTB to the spinal cord for a distance of more than 5 cm just in 2 days. This work exhibits a novel method for nerve visualization by naked eyes and demonstrates the potential for intraoperative navigation.

Keywords: fluorescence; toxin subunit; long time; nerve; cholera toxin; aunds ctb

Journal Title: Acta biomaterialia
Year Published: 2019

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