Coupling of biotin-(poly(ethylene glycol))amine to poly(D,L-lactide-co-glycolide) nanoparticles for versatile surface modification.
Generally, polymeric nanoparticles (NP) for drug targeting are designed to entrap the drug moiety in the core and to present the targeting moiety on the surface. However, in most cases, common preparation techniques of polymeric NP need to be specifically arranged for each compound to be entrapped or attached. In the present work, we introduce a method for versatile conjugation of targeting moieties to the surface of preformed, polymeric NP. Moreover, due to taking advantage of biotin-avidin interactions, our regime opens the additional possibility of a rapid fluorescence labeling of NP. Poly(D,L-lactide-co-glycolide) (PLGA) NP in the size of 210 nm were prepared by the classic oil-in-water method. Such NP were functionalized with biotin-(poly(ethylene glycol))amine (BPEG) by means of cyanuric chloride chemistry. The amount of surface-associated biotin was 850 pmol per milligram of polymer, corresponding to roughly 2650 molecules of biotin per NP. When drawn to scale, such surface coating appeared to be well-suited for subsequent binding of avidin or avidin-linked ligands. By resonant mirror measurements, we could prove specific binding of biotinylated NP to a NeutrAvidin (NAv)-coated surface. Furthermore, after coupling of NAv-linked fluorescence dyes to BPEG-functionalized NP, differences in binding and uptake could be demonstrated using two epithelial cell lines (Caco-2, A549).
Weiss
Barbara
B
Biopharmaceutics and Pharmaceutical Technology, Center for Bioinformatics, Saarland University, Saarbruecken, Germany.
Schneider
Marc
M
Muys
Leon
L
Taetz
Sebastian
S
Neumann
Dirk
D
Schaefer
Ulrich F
UF
Lehr
Claus-Michael
CM
D001360:Avidin / Q000378:metabolism; D001710:Biotin / Q000008:administration & dosage / Q000737:chemistry*; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D019809:Streptavidin / Q000378:metabolism; D013499:Surface Properties
D005456:Fluorescent Dyes; D011108:Polymers; C036963:fluorescein isothiocyante avidin; C093483:neutravidin; D001360:Avidin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D001710:Biotin; D019809:Streptavidin; D016650:Fluorescein-5-isothiocyanate