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Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons

✍ Scribed by Seth A. Townsend; Gilad D. Evrony; Frank X. Gu; Martin P. Schulz; Robert H. Brown Jr; Robert Langer


Book ID
104003623
Publisher
Elsevier Science
Year
2007
Tongue
English
Weight
559 KB
Volume
28
Category
Article
ISSN
0142-9612

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✦ Synopsis


The use of nanoparticles for targeted drug delivery is often facilitated by specific conjugation of functional targeting molecules to the nanoparticle surface. We compared different biotin-binding proteins (avidin, streptavidin, or neutravidin) as crosslinkers to conjugate proteins to biodegradable nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-biotin polymers. Avidin gave the highest levels of overall protein conjugation, whereas neutravidin minimized protein non-specific binding to the polymer. The tetanus toxin C fragment (TTC), which is efficiently retrogradely transported in neurons and binds to neurons with high specificity and affinity, retained the ability to bind to neuroblastoma cells following amine group modifications. TTC was conjugated to nanoparticles using neutravidin, and the resulting nanoparticles were shown to selectively target neuroblastoma cells in vitro. TTCconjugated nanoparticles have the potential to serve as drug delivery vehicles targeted to the central nervous system.


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