Core-satellite assembly of gold nanoshells on solid gold nanoparticles for a color coding plasmonic nanosensor.

We present core-satellite assemblies comprising a solid gold nanoparticle as the core and hollow decahedral gold nanoshells as satellites for tuning the optical properties of the plasmonic structure for sensing. The core-satellite assemblies were fabricated on a substrate via the layer-by-layer assembly of nanoparticles linked by DNA. We used finite-difference time-domain simulations to help guide the geometrical design, and characterized the optical properties and morphology of the solid-shell nanoparticle assemblies using darkfield microscopy, single-nanostructure spectroscopy, and scanning electron microscopy. Plasmon coupling yielded resonant peaks at longer wavelengths in the red to near-infrared range for solid-shell assemblies compared with solid-solid nanoparticle assemblies. We examined sensing with the solid-shell assemblies using adenosine triphosphate (ATP) as a model target and ATP-aptamer as the linker. Binding of ATP induced disassembly and led to a decrease in the scattering intensity and a color change from red to green. The new morphology of the core-satellite assembly enabled plasmonic color-coding of multiplexed sensors. We demonstrate this potential by fabricating two types of assemblies using DNA linkers that target different molecules - ATP and a model nucleic acid. Our work expands the capability of chip-based plasmonic nanoparticle assemblies for the analysis of multiple, different types of biomolecules in small sample sizes including the microenvironment and single cells.

Plasmonic photothermal release of docetaxel by gold nanoparticles incorporated onto halloysite nanotubes with conjugated 2D8-E3 antibodies for selective cancer therapy.

BACKGROUND: Applied nanomaterials in targeted drug delivery have received increased attention due to tangible advantages, including enhanced cell adhesion and internalization, controlled targeted release, convenient detection in the body, enhanced biodegradation, etc. Furthermore, conjugation of the biologically active ingredients with the drug-containing nanocarriers (nanobioconjugates) has realized impressive opportunities in targeted therapy. Among diverse nanostructures, halloysite nanotubes (NHTs) with a rolled multilayer structure offer great possibilities for drug encapsulation and controlled release. The presence of a strong hydrogen bond network between the rolled HNT layers enables the controlled release of the encapsulated drug molecules through the modulation of hydrogen bonding either in acidic conditions or at higher temperatures. The latter can be conveniently achieved through the photothermal effect via the incorporation of plasmonic nanoparticles. RESULTS: The developed nanotherapeutic integrated natural halloysite nanotubes (HNTs) as a carrier; gold nanoparticles (AuNPs) for selective release; docetaxel (DTX) as a cytotoxic anticancer agent; human IgG1 sortilin 2D8-E3 monoclonal antibody (SORT) for selective targeting; and 3-chloropropyltrimethoxysilane as a linker for antibody attachment that also enhances the hydrophobicity of DTX@HNT/Au-SORT and minimizes DTX leaching in body's internal environment. HNTs efficiently store DTX at room temperature and release it at higher temperatures via disruption of interlayer hydrogen bonding. The role of the physical expansion and disruption of the interlayer hydrogen bonding in HNTs for the controlled DTX release has been studied by dynamic light scattering (DLS), electron microscopy (EM), and differential scanning calorimetry (DSC) at different pH conditions. HNT interlayer bond disruption has been confirmed to take place at a much lower temperature (44 °C) at low pH vs. 88 °C, at neutral pH thus enabling the effective drug release by DTX@HNT/Au-SORT through plasmonic photothermal therapy (PPTT) by light interaction with localized plasmon resonance (LSPR) of AuNPs incorporated into the HNT pores. CONCLUSIONS: Selective ovarian tumor targeting was accomplished, demonstrating practical efficiency of the designed nanocomposite therapeutic, DTX@HNT/Au-SORT. The antitumor activity of DTX@HNT/Au-SORT (apoptosis of 90 ± 0.3%) was confirmed by in vitro experiments using a caov-4 (ATCC HTB76) cell line (sortilin expression > 70%) that was successfully targeted by the sortilin 2D8-E3 mAb, tagged on the DTX@HNT/Au.

Multi-Stimuli Nanocomposite Therapeutic: Docetaxel Targeted Delivery and Synergies in Treatment of Human Breast Cancer Tumor.

A versatile breast cancer-targeting nanocomposite therapeutic combining docetaxel (DXL), polyvinyl alcohol (PVA) network for controlled release, and silica-protected magnetic iron oxide nanoparticles (Fe3 O4 NPs) for targeted delivery and gold nanoparticles (AuNPs) for plasmonic photothermal therapy (PPTT) is presented in this work. First, the designed nanocomposite is magnetically directed for cancer-targeted therapy confirmed by computerized tomography (CT) scans. Second, 10% DXL by mass is loaded into PVA, a pH and temperature responsive gel, for controlled release. Third, PPTT is confirmed with Au/Fe3 O4 /PVA-10%DXL using a prototype circulation system and then for tumor treatment in vivo; Au/Fe3 O4 /PVA-10%DXL is conveniently directed and the entrapped DXL is selectively released (≈96%) via the interaction of green and near-infrared (NIR) light with the localized surface plasmon resonance of AuNPs. A 75% cell death is reported from in vitro studies with DXL doses as low as 20 µg mL-1 of Au/Fe3 O4 /PVA-10%DXL, and a 70% tumor growth inhibition is demonstrated by in vivo experiments with the biosafety studies confirming minimal side effects to other organs. Overall, the developed Au/Fe3 O4 /PVA-10%DXL has a strong potential to simultaneously enhance CT imaging contrast together with the targeted delivery of DXL.

Sensing Biomarkers with Plasmonics.

The detection of biomarkers is critical for enabling early disease diagnosis, monitoring the progression, and tracking the effectiveness of therapeutic intervention. Plasmonic sensors exhibit a broad range of analytical capabilities, from the rapid generation of colorimetric readouts to single-molecule sensitivity in ultralow sample volumes, which have led to their increased exploration in bioanalysis and point-of-care applications. This perspective presents selected accounts of recent developments on the different types of plasmonic sensing platforms, the pervasive challenges, and outlook on the pathway to translation. We highlight the sensing of upcoming biomarkers, including microRNA, circulating tumor cells, exosomes, and cell-free DNA, and discuss the opportunity of utilizing plasmonic nanomaterials and tools for biomarker detection beyond biofluids, such as in tissues, organs, and disease sites. The integration of plasmonic biosensors with established and upcoming technologies of instrumentation, sample pretreatment, and data analysis will help realize their translation to clinical settings for improving healthcare and enhancing the quality of life.

LSPR Tuning from 470 to 800 nm and Improved Stability of Au-Ag Nanoparticles Formed by Gold Deposition and Rebuilding in the Presence of Poly(styrenesulfonate).

Stability and precise control over functional properties of metal nanoparticles remain a challenge for the realization of prospective applications. Our described process of shell formation and rebuilding can address both these challenges. Template silver nanoparticles (AgNPs) stabilized by poly(styrenesulfonate) are first transformed with gold deposition, after which the resulting shell rebuilds with the replaced silver. The shell formation and rebuilding are accompanied by large shifts in localized surface plasmon resonance (LSPR) peak position, which enables LSPR tuning in a range from 470 to 800 nm. Furthermore, chemical stability of Au-AgNPs is significantly improved compared to AgNPs due to gold stability. Silver templates of different shapes and sizes were demonstrated to transform to AuAg composite NPs to further extend the accessible LSPR range tuning. Stabilization of template AgNPs with poly(styrenesulfonate), in contrast to commonly used poly(vinylpyrrolidone), was found to be a key factor for shell rebuilding. The developed Au-AgNPs were shown to be advantageous for surface plasmon resonance (SPR) detection and surface-enhanced Raman spectroscopy (SERS) owing to their tunable LSPR and enhanced stability.

Synthesis and sensing properties of D5h pentagonal silver star nanoparticles.

In this work, we use silver decahedral nanoparticle (AgDeNP) seeds to synthesize pentagonal silver stars (AgStDeNPs) and study the sensing properties of these nanoparticles. The regrowth process of AgStDeNPs is kinetically-controlled, so the purity of the seed NPs is critical to avoid secondary deposition in the highly non-equilibrium reduction. To control the regrowth process, surface blocking with sodium polyacrylate (PANa) was implemented. PANa moderates rough silver nanostructures typically obtained by reduction with ascorbic acid. To modulate polymer binding to the surface and thus to tune surface blocking, pH served as a key synthetic parameter. Under optimal regrowth conditions, new sliver was deposited on the highest energy sites of the decahedra - the vertices of the rims - to yield pentagonal stars. The universality of this regrowth process was established with several different seed particles. The sharpness and size of the stellated tips are tunable by the amount of added silver. Gold deposition onto AgStDeNPs enables the preparation of diverse structures with enhanced stability. Ease of transformation, e.g. rounding, of star branches opens a promising venue for enhanced SPR sensing. Also, AgStDeNPs enable femtomolar detection of 5,5-dithiobis(2-nitrobenzoic acid) in SERS.

Symmetry Breaking by Surface Blocking: Synthesis of Bimorphic Silver Nanoparticles, Nanoscale Fishes and Apples.

A powerful approach to augment the diversity of well-defined metal nanoparticle (MNP) morphologies, essential for MNP advanced applications, is symmetry breaking combined with seeded growth. Utilizing this approach enabled the formation of bimorphic silver nanoparticles (bi-AgNPs) consisting of two shapes linked by one regrowth point. Bi-AgNPs were formed by using an adsorbing polymer, poly(acrylic acid), PAA, to block the surface of a decahedral AgNP seed and restricting growth of new silver to a single nucleation point. First, we have realized 2-D growth of platelets attached to decahedra producing nanoscale shapes reminiscent of apples, fishes, mushrooms and kites. 1-D bimorphic growth of rods (with chloride) and 3-D bimorphic growth of cubes and bipyramids (with bromide) were achieved by using halides to induce preferential (100) stabilization over (111) of platelets. Furthermore, the universality of the formation of bimorphic nanoparticles was demonstrated by using different seeds. Bi-AgNPs exhibit strong SERS enhancement due to regular cavities at the necks. Overall, the reported approach to symmetry breaking and bimorphic nanoparticle growth offers a powerful methodology for nanoscale shape design.

Gold-plated silver nanoparticles engineered for sensitive plasmonic detection amplified by morphological changes.

Gold-plated silver nanoparticles have been developed to undergo morphological changes that enhance the surface plasmon resonance (SPR) sensing response. These morphological changes were realized through thin-frame gold plating that both reinforces the nanoparticle edges and enables partial silver etching upon exposure to several biological molecules, including thiols and amines.

Stable ligand-free stellated polyhedral gold nanoparticles for sensitive plasmonic detection.

Ligand-free stellated gold nanoparticles (AuStNPs) with well-defined octahedral (O(h)) and icosahedral (I(h)) core symmetries were prepared using hydrogen peroxide as a reducing agent. Only three reagents: gold precursor (HAuCl4), H2O2 and NaOH were required to form colloidally and chemically stable AuStNPs with a zeta-potential between -55 and -40 mV indicative of excellent charge stabilization. The size and degree of stellation of AuStNPs can be controlled by several synthetic parameters so that the localized surface plasmon resonance (LSPR) can be varied from ca. 850 nm in near-infrared (NIR) to ca. 530 nm. In particular, AuStNP size and LSPR tuning can be conveniently accomplished by iodide variation. The size distribution of AuStNPs was improved by nucleation with ascorbic acid, and the AuStNP size and degree of branching could be readily modified using arginine. AuStNPs are advantageous for SPR sensing, as it was demonstrated in the sensitive detection of not only thiols, such as ampicillin, but also iodide with the detection limit of 3.2 pM (0.4 ng L(-1)). The reported ligand-free stable AuStNPs thus should be very useful for biodiagnostics based on SPR sensing and potentially for SERS and hyperthermia therapy.

Multifaceted prismatic silver nanoparticles: synthesis by chloride-directed selective growth from thiolate-protected clusters and SERS properties.

We describe the synthetic preparation of well-defined symmetric multifaceted prismatic silver nanoparticles with chemically controlled faceting advantageous for strong and tunable surface-enhanced Raman scattering, SERS. These silver nanoparticles, that have been termed nanoflowers, AgNFls for their characteristic morphologies, have been prepared by a one-pot aqueous reaction under ambient conditions. AgNFl faceting is synthetically controlled by selective nanoparticle growth driven by chloride ions. Selective chloride binding to the surface of growing AgNFls results in nanoparticle enlargement predominantly at the points of their highest energy. These growth points are located at the tips of prismatic polygons in precursor prismatic morphologies that have been produced from thiolate-protected silver clusters whose coalescence is triggered with a strong base. For the practical aspects of AgNFl synthesis, concentrations of thiol and a strong base were found to be the key variables reliably controlling the extent of AgNFl faceting, as well as the kinetics of AgNFl formation and their stability. The selective growth of AgNFls progresses slower compared to that of non-faceted prisms: fewer nuclei can form leading to larger AgNFls with the diameter ranging from 130 to 2250 nm and asperity sizes on the order of 20 to 100 nm. Self-assembly of AgNFls yields columnar stacking. AgNFls were demonstrated to function as a promising substrate for surface-enhanced Raman scattering. SERS measurements were performed for a series of AgNFls with variable faceting, where the enhancement factors of 4.6 × 10(8) and 425 have been achieved for dry solid films and aqueous dispersions of non-aggregated AgNFls with single-particle enhancement, respectively. These SERS results are promising, especially in combination with that AgNFl nanoscale asperities can be conveniently tailored synthetically. Overall, AgNFls offer valuable opportunities for a system with synthetically variable nanoscale asperities.

Monodisperse hexagonal silver nanoprisms: synthesis via thiolate-protected cluster precursors and chiral, ligand-imprinted self-assembly.

Silver nanoprisms of a predominantly hexagonal shape have been prepared using a ligand combination of a strongly binding thiol, captopril, and charge-stabilizing citrate together with hydrogen peroxide as an oxidative etching agent and a strong base that triggered nanoprism formation. The role of the reagents and their interplay in the nanoprism synthesis is discussed in detail. The beneficial role of chloride ions to attain a high degree of reproducibility and monodispersity of the nanoprisms is elucidated. Control over the nanoprism width, thickness, and, consequently, plasmon resonance in the system has been demonstrated. One of the crucial factors in the nanoprism synthesis was the slow, controlled aggregation of thiolate-stabilized silver nanoclusters as the intermediates. The resulting superior monodispersity (better than ca. 10% standard deviation in lateral size and ca. 15% standard deviation in thickness (<1 nm variation)) and charge stabilization of the produced silver nanoprisms enabled the exploration of the rich diversity of the self-assembled morphologies in the system. Regular columnar assemblies of the self-assembled nanoprisms spanning 2-3 µm in length have been observed. Notably, the helicity of the columnar phases was evident, which can be attributed to the chirality of the strongly binding thiol ligand. Finally, the enhancement of Raman scattering has been observed after oxidative removal of thiolate ligands from the AgNPR surface.

Ultrathin gold nanoframes through surfactant-free templating of faceted pentagonal silver nanoparticles.

Ultrathin gold nanoframes (up to 1.6 nm) were prepared via templating upon well-defined faceted silver morphologies. Starting with silver decahedra, small quantities of gold (1-10 mol% relative to the amount of silver) were selectively deposited on the nanoparticle edges under optimized reducing conditions. Silver dissolution in hydrogen peroxide yielded well-defined gold frames that retained their structural integrity in the ultrathin nanowire regime below 2 nm. The frame formation protocol was also successfully applied to other silver nanoparticle shapes featuring pentagonal twinning and (111) facets (e.g., pentagonal faceted rods and icosahedra). The demonstrated approach can be applied in the controlled preparation of ultrathin metal nanowires complementary to lithography and in the production of ultrafine noble-metal nanostructures for catalytic applications.

Silver nanoparticles with planar twinned defects: effect of halides for precise tuning of plasmon resonance maxima from 400 to >900 nm.

We studied effects of halides on morphology of planar twinned silver nanoparticles and demonstrated application of these effects to precisely tune silver surface plasmon resonance maxima in a broad vis-NIR range using a reliable two-stage modification protocol.

Chiral thiol-stabilized silver nanoclusters with well-resolved optical transitions synthesized by a facile etching procedure in aqueous solutions.

A novel approach of cyclic reduction in oxidative conditions has been developed to prepare a single dominant species of chiral thiol-stabilized silver nanoclusters (AgNCs). Such AgNCs, which are stable in solution for up to a few days, have been obtained for the first time. The generality of the established procedure is proven by using several enantiomeric water-soluble thiols, including glutathione, as protective ligands. The prepared AgNCs featured prominent optical properties including a single pattern of UV-vis absorption with well-resolved peaks. The chirality of the clusters has been investigated by circular dichroism (CD) spectroscopy. CD spectra displayed strong characteristic signatures in the visible range. Tentative identification of the cluster composition is discussed.