Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons.
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. TTC-conjugated nanoparticles have the potential to serve as drug delivery vehicles targeted to the central nervous system.
Townsend
Seth A
SA
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Evrony
Gilad D
GD
Gu
Frank X
FX
Schulz
Martin P
MP
Brown
Robert H
RH
Langer
Robert
R
D001672:Biocompatible Materials / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D019921:Biotinylation; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013744:Tetanus Toxin / Q000737:chemistry*
D001672:Biocompatible Materials; D011108:Polymers; D013744:Tetanus Toxin; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D001710:Biotin