Gold nanoparticles with specific optical properties in combination with the CLPFFD peptide that exhibits selectivity for β-amyloid (Aβ) aggregates are promising photothermal absorbers for application in Alzheimer's disease therapy. We report on hollow gold nanospheres (HAuNS) and gold nanorods (AuNR), which exhibit strong plasmonic near infrared (NIR) absorbance in the optical window of biological tissue and which are functionalized with CLPFFD in two different ways. Therefore the peptide was either directly bound to the particle surface or indirectly to a particle-protecting polyethylene glycol (PEG) ligand shell, thereby reducing the CLPFFD density on the surfaces of both types of particles. Fully PEGylated particles were used for comparison. The effects on cell viability and the fundamental suitability of the HAuNS and AuNR conjugates as photothermal absorbers to inhibit Aβ-fibrillation are analysed in vitro. The positive influence of the use of PEG ligands on the reduced cytotoxicity of the conjugates and on the Aβ-disaggregation is discussed.

We studied the effect of gold nanoparticle (AuNP) size, surface charge, concentration and morphology on the integrity of the blood–brain barrier (BBB) in a well-established in vitro model set-up. We focused on the effect of peptide functionalized hollow gold nanospheres and gold nanorods, which selectively bind to amyloidogenic β-amyloid structures. These AuNP conjugates have already been successfully tested as photothermal absorbers for potential application in Alzheimer's disease (AD) therapy in an in vitro set-up, but may exhibit a low passage through the BBB due to their overall negative charge. Our results show that: (i) small (1.4 nm) AuNPs strongly affects the BBB integrity, (ii) negative surface charge impedes BBB passage, and (iii) this charge effect caused by the peptide is compensated by covalent coupling to a polyethylene glycol ligand stabilizing the particles in diluted manner.

In this work the effect of multivalency on the stability of NIR-absorbing HAuNSs and AuNRs functionalized by mono-, bi- and tridentate polyethyleneglycol (PEG) thiol ligands is reported. Comparison of commercially-available monodentate and self-synthesized bi-and tridentate methoxy terminated thiol-polyethyleneglycol ligands having molecular weights of around 5000 Da shows the stability increase of HAuNSs and AuNRs for bi-and tridentate ligands, attributed to the multivalency of the ligands. The stability was explored according to three different aspects: (1) stability towards competition reactions with the strong binding ligand dithiothreitol, (2) resistance towards oxidative Au dissolution with potassium cyanide, and (3) colloidal stability, tested by the addition of NaCl. Our PEGylation approach leads to AuNRs where the CTAB concentration is below the detection limit of the performed analytical methods, which is vital for any clinical applications. Furthermore, we found strikingly high biocompatibility after PEGylation for both particle types whereby we observed no significant difference in cytotoxicity comparing the mono-, bi-and tridentate PEGylated species.

We report an experimental finding of photoacoustic signal enhancement from finite sized DNA–gold nanoparticle networks. We synthesized DNA-functionalized hollow and solid gold nanospheres (AuNS) to form finite sized networks, which were characterized by means of optical extinction spectroscopy, dynamic light scattering, and scanning electron microscopy in transmission mode. It is shown that the signal amplification scales with network size for networks comprising either hollow or solid AuNS as well as networks consisting of both types of nanoparticles. The laser intensities applied in our multispectral setup (λ = 650 nm, 850 nm, 905 nm) were low enough to maintain the structural integrity of the networks. This reflects that the binding and recognition properties of the temperature-sensitive cross-linking DNA-molecules are retained.