Completely Dispersible PEGylated Gold Nanoparticles under Physiological Conditions:  Modification of Gold Nanoparticles with Precisely Controlled PEG-b-polyamine

Abstract

A novel water-soluble, biocompatible polymer, poly(ethylene glycol)-block-poly((2-N,N-dimethylamino)ethyl methacrylate) (PEG-b-PAMA), possessing controlled molecular weight with a narrow molecular weight distribution, was synthesized by the atom-transfer radical polymerization (ATRP) method. PEG-b-PAMA having a short PAMA chain length was successfully synthesized under suitable polymerization conditions. Gold nanoparticles (GNPs) were modified using PEG-b-PAMA prepared under a variety of PEGylation conditions. Under alkaline conditions (pH >10) and an [N]/[GNP] ratio of more than 3300, the PEGylated GNPs (PEG-GNPs) showed complete dispersion stability, avoiding coagulation. The amino groups of the PAMA segment of the block copolymers were completely deprotonated above pH 10. This means that PEG-b-PAMA interacted with the GNP surface via multipoint coordination of the tertiary amino groups of PAMA, not electrostatically. The effect of the number of amino groups in the PAMA segment on GNP surface modifications was investigated by zeta potential and dynamic light scattering (DLS) measurements. When the PEG-GNPs were prepared in excess polymer solution, almost the same diameter was observed regardless of the PAMA chain length. After the PEG-GNPs were purified by centrifugation, the zeta potentials of all PEG-GNPs were shielded to almost 0 mV, indicating the effective modifications of the GNP surface by PEG-b-PAMA regardless of the chain length. However, the particle size and particle size distribution of the purified PEG-GNPs were strongly affected by the PAMA chain length. PEG-GNPs with longer PAMA segments underwent coagulation after purification, whereas PEG-GNPs with shorter PAMA segments increased their dispersion stability. The experimental results of the thermal gravimetric analysis confirmed that the PEG density on the GNP surface increased as the AMA units decreased to 3. Thus, the dispersion stability depended significantly on the PEG density on the GNP surface. GNPs modified with PEG-b-PAMA having short AMA units showed excellent dispersion stability under a variety of pH conditions. The excellent dispersion stability of the obtained PEG-GNP was also confirmed both in bovine serum albumin (BSA) solution and 95% human serum.

Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance

“…We have already confirmed the usefulness of the oligoamine anchor 15,16,26,27,56,[72][73][74][75][76] instead of the sulfanyl group anchor [77][78][79] for molecular immobilization on gold surfaces and developed polyamineended PEG-modified gold surfaces using PEG-block-poly [2- Densely PEG-chain-tethered biointerface Y Nagasaki platform for ssDNA immobilization and detection; 73 in our scheme, PEG-b-PAMA was immobilized onto the gold surface followed by treatment with a ssDNA-SH, resulting in the formation of ssDNA-SH/ PEG-b-PAMA co-immobilized gold surface.…”

“…In this study and our companion article, 80 we reported for the first time the direct observations of homogeneous/ inhomogeneous distributions of PEG and polyamine segments in the polymer layers on flat gold surfaces, where polyamine segments functioned as an anchor for molecular immobilization on the surface and at least six units of amine groups were needed for the strong chemisorption of polyamine on a gold substrate. 26 Using PEG-b-PMA block copolymers with different chain lengths, we then prepared an ssDNA/PEG-b-polyamine hybrid surface on a gold surface. It is interesting to note that the PEG-b-PAMA modification increased the amount of immobilized ssDNA-SH on the gold surface to 2-5 times as much as that on a bare gold surface, where the effective and selective detection of the complementary ssDNA was accomplished by the ssDNA-SH/PEG-b-PAMA (5k/5k) co-immobilized surface.…”

“…This is especially true regarding the versatile techniques for surface coating using PEG that have been developed since the 1980s to improve blood and bio-compatibility. Figure 1 summarizes several methods for the immobilization of PEG on substrate surfaces: PEG gels, 19,20,36 the physical and chemical immobilization of PEG 13,21,37 (so-called grafting-to method), the adsorption of block [22][23][24][25][26][27]38 and graft 27,28,39,40 copolymers, polymerization from the surface 41 (the so-called grafting-from method), the immobilization of star-shape polymers and micelles, [42][43][44] and other methods.…”

“…The present review describes the effect of mixed PEG on the non-biofouling character and also hybrid construction of a PEG/biopolymer mixture on substrate surfaces for versatile applications. Because many excellent reviews on PEG surface coating have been previously published, [15][16][17][18][19][20][21][22][23][24][25][26][27][28] this review mainly introduces our work. BACKGROUND PEG has long been manufactured industrially and utilized in many applications such as nonionic surfactants, lubricants, an intermediate for urethane composition, adhesives and cosmetics.…”

Engineering of poly(ethylene glycol) chain-tethered surfaces to obtain high-performance bionanoparticles

“…To further characterize the state of the polymer on the GNP surface, commercial GNPs were modified using PEG-b-PAMA prepared under various PEGylation conditions [49]. In alkaline media (pH > 10) and with a [N]/[GNP] ratio above 3300, the dispersions of PEGylated GNPs were highly stable against coagulation.…”