Characterization of Nickel-Decorated PLGA Particles Anchored with a His-tagged Polycation

Abstract

The pharmacological impact of oligodeoxynucleotides (ODN) as transcription factors decoys (anti-sense) depends on the efficiency of cellular uptake. In this study, we sought to generate nickel-decorated particles to facilitate the entry of ODN into dendritic cells (DCs), the primary instigators of immune responses. Nickel ions were incorporated into the matrix of poly(D,L-lactide-co-glycolide) (PLGA) particles using the metal chelating lipid DOGS-NTA-Ni. Submicrometer-sized PLGA particles containing nickel ions (PLGA-Ni) were formed using a double-emulsion solvent evaporation method. Infrared spectroscopy provided chemical proofs of nickel incorporation into the PLGA matrix. Binding of the polycation O10H6 raised the surface potential of PLGA-Ni from -17 mV to +13 mV. This change was partially reserved by the presence of free imidazole, suggesting the binding was mediated by nickel-histidine coordination. When compared to PLGA particles without nickel, ODN bound to O10H6-coated PLGA-Ni particles exhibited enhanced capacity to accumulate in DCs cultured in vitro. DCs exhibited cellular stress after exposure to PLGA-Ni complexed with O10H6 and DNA, but this effect can be prevented by serum and was reversed overnight. These data suggest PLGA-Ni should be further explored as a nucleic acid carrier in the context of anti-sense gene down-regulation.

Immune Cells Activating Biotin-Decorated PLGA Protein Carrier

“…The particles were formed by coemulsifying PLGA polyester and DSPE-PEG-biotin lipid using methods previously described. 33 Two mixing ratios of PLGA to biotin-lipid (100:1 and 10:1, w/w) were selected based on preliminary experiments conducted to identify formulations in which particle stability and binding capacity for avidin were mutually optimized. The resulting particles were analyzed using dynamic light scattering whereby a monodispersed population (with respect to size) was revealed (Figure 2A).…”

“…The nanosized particles, referred to as biotinylated nanoparticles (bNPs), are prepared from coemulsifying PLGA (50:50) and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[biotinyl­(polyethylene glycol)-2000] (DSPE-PEG(2000)-biotin), resulting in a biotin-decorated particle surface. We and others have demonstrated that surface adsorption on nanoparticles is an efficient method for delivering biologics into antigen presenting cells (APCs). − The surface loading method circumvents the denaturing effects during encapsulation and polymer erosion. In this design, biotinylated proteins can be anchored on bNP via tetravalent avidin ( K D ∼ 10 –15 M).…”

Synthesis of poly(N-isopropylacrylamide) particles for metal affinity binding of peptides

“…The bound His 6 -tag can be released upon the addition of imidazole that acts as a competitive ligand to displace the bound His 6 -tag [29]. The affinity of the His 6 -tag to chelated metal ions has been exploited to attach proteins or peptides to various micro- or nano-particles, including polystyrene particles [30], poly(lactic- co -glycolic acid) particles [31], polyketal particles [32], and magnetic nano-particles [33] but has not been used previously with PNIPAM particles.…”