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Neuronal cell targeting using liposome‐coupled botulinum toxin heavy chain
Author(s) -
Tabaku Lindita Sait,
Richards Roberta L.,
Patel Ankit V.,
Yarlagadda Jay K.,
Spadaro John A.,
Gordon Richard K.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.762.5
Subject(s) - liposome , phosphatidylserine , flow cytometry , chemistry , phospholipid , ganglioside , receptor , microbiology and biotechnology , biophysics , pharmacology , biochemistry , membrane , biology
Our goal is a liposomal delivery system of membrane‐linked botulinum toxin type B heavy chain (BoNT/B HC) to specifically target therapeutics to neuronal cells. Unilamellar liposomes (~200 nm) containing egg phosphatidylcholine, sphingomyelin, cholesterol, and cholest‐5‐en‐3β [dithiopyridine] (to couple HC SH group to liposomes) were prepared by extrusion. Coupling of BoNT HC to the liposomal surface was verified by flow cytometry (FC) using liposomes containing Rhodamine‐labeled phospholipid (N‐Rh‐PE) and FITC‐labeled HC. FC was used to determine binding specificity of liposomes with or without coupled BoNT‐HC to SH‐SY5Y (neuronal cells) or PC12 cells (control cells lacking BoNT/B receptors). N‐Rh‐PE‐liposomes with or without coupled FITC‐HC were incubated with cells and cell‐associated fluorescence determined. Liposomes alone did not bind to either cell line until >45 min of incubation. Free HC or liposomes coupled to BoNT HC bound to the SH‐SY5Y cells, but not to control PC‐12 cells except when the cells loaded with the BoNT/B ganglioside receptor GT1b. Since liposomes can deliver encapsulated drugs to cells, our BoNT/B HC‐coupled liposomes form the basis for delivery of BoNT therapeutics to intoxicated neuronal cells. The opinions or assertions are the private views of the authors, and not official views of the Department of the Army or the Department of Defense. Supported by DTRA 3.10032_08_WR_B.