Ultrasmall AuNPs Research Articles

Expanding the Toolbox of Oxidants: Controllable Etching of Ultrasmall Au Nanoparticles toward Tailorable NIR-II Luminescence and Ligand-Mediated Biodistribution and Clearance.

Oxidant-driven and controllable etching of small-sized nanoparticles (NPs, d < 3 nm) and tailorable modulation of their optical properties are challenging due to the high reactivity and complicated surface chemistry. Herein, we present a facile strategy for highly controllable oxidative etching of ultrasmall AuNPs and tailorable modulation of luminescence. The proper choice of a moderate oxidant, ClO-, could not only selectively etch the Au(I)-thiolate motifs from the nanoparticle surface at the subnanometer scale but also retained a stable metallic core structure without aggregation, which impressively prompted the wide-range luminescent switching from the visible to second near-infrared (NIR-II) region. The resultant oxidized AuNPs displayed highly luminescent NIR-II emission with a quantum yield of 3.0%, excellent monodispersed stability, ideal biocompatibility, and tunable shielding effects against protein adsorption. With those outstanding features, oxidized AuNPs could be utilized as nanoprobes for long-lasting and in vivo bioimaging of associated metabolic behaviors with distinguishable organ-specific targeting capabilities and ligand-mediated kinetics in nanoparticle clearance. These findings expand the toolbox of oxidants for the controllable synthesis of NIR-II nanoprobes and open up a path for exploring diverse ligand interactions on ultrasmall AuNPs with organs or tissues that might advance their monitoring applications for a wide range of clinically important diseases.

Mxene-based capacitive enzyme-free biofuel cell Self-Powered sensor for lead ion detection in human plasma

In response to the health risks posed by heavy metal lead, we have developed a self-powered sensor specifically designed for detection of lead ions in this work. This sensor is designed based on an enzyme-free biofuel cell as a self-powered source. The biofuel cell utilizes two-dimensional lamellar Au NPs-Ti3C2Tx heterostructures as the capacitive anode substrate material. The Ti3C2Tx MXene with the excellent charge storage capacity and fast discharge characteristics, provides a large instantaneous current for signal amplification. Furthermore, the DNA walker technique was combined to regulate the loading of ultra-small Au NPs exhibiting glucose oxidase-like properties. Meanwhile, Co, Mn nitrogen-doped carbon-based nanosheets were designed as the cathode with outstanding oxygen reduction reaction catalytic activity. As a result, the constructed enzyme-free biofuel cell has been used to detect Pb2+ with a wide linear range (0.01–7500 nM) and a low detection limit (0.43 pM). It has been successfully applied to the determination of Pb2+ in human plasma, achieving excellent recovery rates (94.0–110.5 %). The developed capacitive anodes not only significantly optimized the performance of the biofuel cell self-powered sensors, but also provided important insights for the future design and construction of biofuel cells.

Straightforward microwave-assisted synthesis of ultrasmall gold nanoparticles acnhored on reduced graphene oxide for enhanced antibacterial application

Graphene derivative materials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have garnered significant attention from scientists for over two decades due to their distinctive characteristics and versatile applications across various fields, particularly in biomedical applications. Incorporating gold nanoparticles (AuNPs) into rGO sheets as rGO-Au nanocomposites further enhances its performance in biomedical applications. This study presents a rapid and efficient method for synthesizing ultrasmall AuNPs anchored on reduced graphene oxide (rGO-Au) using microwave irradiation and ascorbic acid. The optimum microwave treatment was 4 min, ensuring the highest GO reduction degree. Structural characterization by TEM reveals a distinctive architecture with ultrasmall AuNPs (average size of 2.2 nm) distributed on the rGO sheets. Interestingly, while the synthesized rGO-Au did not exhibit any antibacterial activities against both Escherichia coli and Staphylococcus aureus in disk diffusion assays, it demonstrated bacteriostatic effect at remarkably low concentrations when assessed by optical density measurement. The effective concentration of rGO-Au to inhibit E. coli growth was determined to be 2.5 ppm, while for S. aureus, it was 5 ppm, resulting in growth inhibition of 53.1% and 50.0%, respectively. These findings provide a straightforward synthesis route for rGO-Au nanocomposites and underscore the importance of AuNPs’ size and quantity in modulating antibacterial properties.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level.

Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level

AbstractUltrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure–property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near‐infrared window using a phosphorothioate‐modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411‐functionalized AuNPs (AS1411‐AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor‐targeting efficiencies but also the subcellular transport of AS1411‐AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor‐targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor‐targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Metal-organic framework-modulated Fe3O4 composite au nanoparticles for antibacterial wound healing via synergistic peroxidase-like nanozymatic catalysis

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Ultrasmall Au/Pt-loaded biocompatible albumin nanospheres to enhance photodynamic/catalytic therapy via triple amplification of glucose-oxidase/catalase/peroxidase

The weak catalytic activity of nanocatalysts and the insufficient endogenous hydrogen peroxide (H2O2) in tumor microenvironment (TME) seriously restricted the efficacy of catalytic therapy, and the non-degradability of inorganic nanocarriers was also unfavorable for their clinical applications. Herein, by depositing gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) with ultrasmall size and modifying photosensitizer (IR808), a biocompatible bovine serum albumin (BSA) nanoplatform (BSA@Au/Pt-IR808) with triple-amplification of enzyme activity was constructed to enhance photodynamic therapy (PDT) and catalytic therapy. Ultrasmall AuNPs possessed glucose oxidase (GOx)-like activity, by which the self-supplying H2O2 accelerated the dual-enzyme activity of peroxidase (POD) and catalase (CAT) of ultrasmall PtNPs, promoting the generation of hydroxyl radical (·OH) and singlet oxygen (1O2). Compared with BSA-IR808 and BSA@Pt, the yields of 1O2 and ·OH of BSA@Au/Pt-IR808 increased by 38.2% and 18.6%. Under the combination action of photothermal therapy (PTT)/PDT/catalytic therapy of BSA@Au/Pt-IR808, the cell viability significantly reduced to 12.8%, and the tumors were completely eliminated, demonstrating the enhanced PDT and catalytic therapy against breast cancer.

Rapid biosynthesis and characterization of metallic gold nanoparticles by olea europea and their potential application in photoelectrocatalytic reduction of 4-nitrophenol

In recent years, photoelectrocatalysis of gold nanoparticles (Au NPs) has received considerable attention due to their potential to improve catalytic efficiency. Herein, ultra-small Au NPs were successfully synthesized in a single pot using olea europea leaf extract as a green reducing agent for the degradation of 4-nitrophenol. The TEM images showed uniform distribution and spherical shape of Au NPs with an average diameter of 5 nm. Taking advantage of the ability of Au nanoparticles to absorb visible and near-infrared light, 4-nitrophenol can be successfully reduced in the presence of NaBH4. Additionally, the electrochemical activity of the fabricated Au photocathode was investigated by linear sweep voltammetry in the dark and at VIS-NIR light irradiation. This showed an increased photocurrent density of 27 mA cm−2 with an onset potential of −0.71 V. This indicates that the Au photocathode is highly active at VIS-NIR light. Interestingly, the Au photocathode showed a higher current density of 37 mA cm−2 with an onset potential of −0.6 V in the presence of 4-nitrophenol during VIS-NIR irradiation, indicating that 4-nitrophenol was efficiently reduced by the photocathode. The Au photocathode completely reduced 4-nitrophenol in the wastewater within 35 min. Recyclability studies showed that the Au NPs photocathode exhibited higher stability over multiple cycles, confirming the ability of the electrode to treat wastewater over a longer period of time. This study demonstrates the effectiveness of the photoelectrochemical (PEC) process in reducing organic compounds in wastewater.

Glucose-responsive mesoporous prussian blue nanoprobes coated with ultrasmall gold and manganese dioxide for magnetic resonance imaging and enhanced antitumor therapy

To achieve safe and efficient tumor therapy, it was a powerful strategy of constructing an intelligent tumor microenvironment (TME)-responsive nanoprobe. In this study, by coating ultrasmall gold nanoparticles (AuNPs) and manganese dioxide (MnO2) on mesoporous prussian blue (MPB), MPB@AuNPs@MnO2 nanoprobe with H2O2 self-generation was developed for magnetic resonance (MR) imaging, photothermal therapy (PTT) and enhanced chemodynamic therapy (CDT). The results indicated that the prepared MPB@AuNPs@MnO2 possessed uniform size and good biocompatibility. Using glucose-responsive self-supplying H2O2 of ultrasmall AuNPs, and glutathione (GSH)-responsive Mn2+ release from MnO2 degradation, the accelerated hydroxyl free radicals (·OH) generation efficiency (80.0 % to 90.84 %) and enhanced MR relaxation (1.93 to 9.96 mM−1·s−1) were achieved. Importantly, the prepared MPB@AuNPs@MnO2 exhibited excellent photothermal performance with a photothermal conversion efficiency of 42.62 %. Moreover, the intracellular H2O2/·OH generation was demonstrated, and the in vitro CDT/PTT was enhanced, by which the cell viability was reduced to 6.4 %, stronger than 18.8 % of MPB@MnO2. By modeling MDA-MB-435 tumor-bearing nude mice, the combined CDT/PTT of MPB@AuNPs@MnO2 nanoprobe greatly inhibited the tumor growth, and after 15 days, the tumor completely disappeared. This work provided a promising strategy to develop TME-responsive self-supplying H2O2 nanoprobe, achieving MR imaging and enhanced antitumor efficacy.

Ultrasmall-in-Nano: Why Size Matters.

Gold nanoparticles (AuNPs) are continuing to gain popularity in the field of nanotechnology. New methods are continuously being developed to tune the particles’ physicochemical properties, resulting in control over their biological fate and applicability to in vivo diagnostics and therapy. This review focuses on the effects of varying particle size on optical properties, opsonization, cellular internalization, renal clearance, biodistribution, tumor accumulation, and toxicity. We review the common methods of synthesizing ultrasmall AuNPs, as well as the emerging constructs termed ultrasmall-in-nano—an approach which promises to provide the desirable properties from both ends of the AuNP size range. We review the various applications and outcomes of ultrasmall-in-nano constructs in vitro and in vivo.

Multifunctional Human Serum Albumin Fusion Protein as a Docetaxel Nanocarrier for Chemo-photothermal Synergetic Therapy of Ovarian Cancer.

Modification of inorganic nanoparticles with human serum albumin (HSA) that load with chemotherapeutic agents has been reported to conduct chemo-photothermal synergistic therapy of tumors. However, loading some highly insoluble drugs would cause the conformation disorder of HSA, which is unable to give full play to tumor targeting and biological compatibility. Besides, inorganic nanoparticles with too large of a size would appear with unsatisfactory metabolism and lead to biological toxicity. Herein, the recombinant protein integrating histidine (His), HSA, enzyme responsive site, and arginine-glycine-aspartic acid (RGD) by genetic engineering technology was developed to co-load docetaxel (DTX) and gold nanoparticles (Au NPs) to construct RHMH18@AuD NPs. In which, DTX was encapsulated in the micelle part that self-assembled by histidine, while ultrasmall Au NPs were clustered in the HSA part through biomimetic mineralization. RHMH18@AuD NPs could maintain a consistent conformation with HSA and a uniform dispersion in saline. In vitro experiments verified that RHMH18@AuD NPs could target cancer cells followed by being structurally separated into RGD-HSA@Au and His@DTX under the restriction of MMP-2 enzymes. In vivo results verified the favorable biocompatibility and positive chemo-photothermal synergetic therapy efficiency of RHMH18@AuD NPs on a human ovarian tumor.

In vivo bio-distribution and acute toxicity evaluation of greenly synthesized ultra-small gold nanoparticles with different biological activities

Ultra-small gold nanoparticles (Au-NPs) “≤ 10 nm diameters” have potent biomedical applications. Hence, the present study aimed to greenly synthesize ultra-small gold nanoparticles using Egyptian propolis extract. Different biological activities, in vivo bio-distribution and acute toxicity study were assessed. Results revealed that, Egyptian propolis extract can successfully synthesize the highly pure and stable ultra-small Au-NPs with average diameter 7.8 nm. In vitro antimicrobial and antimycobacterial activities revealed the powerful effect of the prepared Au-NPs. Moreover, the cytotoxic effect on human cancer cell lines revealed the potent inhibition of the cancer cells’ proliferation with high reactive oxygen species-mediated apoptosis induction. In vivo bio-distribution and acute toxicity studies were performed (10 and 100 mg/kg doses) in male albino rats. The ultra-small Au-NPs showed low or no toxicity upon using the Au-NPs low dose. The mean area accumulation (%) of the Au-NPs was higher in the liver, kidney, and brain tissues (4.41, 2.96, and 0.3 times, respectively) treated with high Au-NPs dosage compared to those treated with the low dose. Surprisingly, Au-NP accumulation in brain tissue was observed in the glial cells only. Accordingly, the low dose (10 mg/kg) of Au-NPs can be used safely in a variety of biomedical applications.

The radiation-induced preparation of ultrasmall gold nanoparticles in Au(III) complexes with units of poly(1-vinyl-1,2,4-triazole) and poly(1-vinyl-1,2,4-triazole) – poly(acrylic acid)

Gold nanoparticles (AuNPs) with average sizes of 1.5 nm and 3 nm and narrow size distribution have been prepared in the irradiated aqueous solutions and suspensions of Au(III)-complexes with units of poly(1-vinyl-1,2,4-triazole) (PVT) and poly(1-vinyl-1,2,4-triazole) – poly(acrylic acid) (PAA) respectively. The formation of AuNPs has been studied using UV-VIS spectroscopy and transmission electron microscopy. The effective stabilization of ultrasmall AuNPs is achieved due to the combination of both electrostatic interaction of polymer units and the specific adsorption of functional groups on the nanoparticle surface. The radiation-chemical approach makes it possible to obtain nanoparticles of a controlled size and containing no impurities of chemical reducing agents.

Gold nanoparticles spontaneously grown on cellulose nanofibrils as a reusable nanozyme for colorimetric detection of cholesterol in human serum

Recently, gold nanoparticles (AuNPs) are extensively used as peroxidase mimics. However, low catalytic activity, high synthesis cost, substrate-induced aggregation in reaction medium and difficulty in recovery and reuse still remain as major challenges. Here, a novel, simple, spontaneous, and reagent-less in-situ method for the production of AuNPs using dialdehyde cellulose nanofibrils (DACNF) is proposed. AuNPs synthesis time and size were greatly influenced by aldehyde content and the optimal aldehyde content for ultra-small AuNPs (≈10 nm) was 2.1 mM/g. AuNPs@DACNFs exhibited broad-spectrum peroxidase activity and steady-state kinetics revealed their better kinetic parameters (low Km and high Vmax) over horseradish peroxidase (HRP). AuNPs@DACNFs was further converted into paper strip, which served as a biosensor for H2O2 and cholesterol detection. The proposed method exhibited wide linear response in the range of 10–90 μM and 0.05–0.45 mM, and detection limit of 0.39 μM and 1.9 μM for H2O2 and cholesterol, respectively. Great shelf life and reusability were evident by FE-SEM and ICP-OES analysis. The smartphone application “Color Grab” was used to enable the portable onsite detection. The results of cholesterol detection in human serum samples were in agreement with clinically observed values, suggesting the great potential of the probe in disease diagnosis.

Nanozyme catalyzed cascade reaction for enhanced chemodynamic therapy of low-H2O2 tumor

The efficacy of chemodynamic therapy (CDT) is strongly dependent on the hydrogen peroxide (H2O2) level of tumor tissues. Nanozyme-mediated glycolysis reaction is considered as a promising way to supply the amount of H2O2in situ, therefore, the development of nanozyme-based CDT platform is desirable for low-H2O2 tumor treatment. Herein, we developed a hybrid nanozyme (denoted as MMF-Au) composed of ultrasmall gold nanoparticles (Au NPs) and melanin-coated manganese dioxide flowers (MMF) for enhanced CDT of low-level H2O2 tumors under the guidance of magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). The MMF-Au nanozyme could trigger the cascade reaction of glucose oxidation and Fenton-like reaction. First, the ultrasmall Au NPs with glucose oxidase (GOx)-mimic activity could catalyze the oxidation of glucose to generate large amount of H2O2. Subsequently, the H2O2 was converted into highly toxic hydroxyl radicals (•OH) via a Mn2+-mediated Fenton-like reaction, due to the release of Mn2+ during the decomposition of MMF in tumor acid microenvironment. Meanwhile, the released Mn2+ could perform T1-weighted MRI. Additionally, the MMF-Au could be used for PAI and photothermal therapy (PTT) due to the strong absorption of melanin in the near-infrared (NIR) region. Both in vitro and in vivo experimental results demonstrated that nanozyme catalyzed cascade reaction could achieve better CDT efficacy in tumors with low level of H2O2. This study provided a promising strategy to construct nanozyme-triggered cascade reaction system against low-level H2O2 tumors.

Concentration‐Dependent Subcellular Distribution of Ultrasmall Near‐Infrared‐Emitting Gold Nanoparticles

AbstractThe ability to accurately control the subcellular distribution of nanomedicines provides unique advantages on understanding of cellular biology and disease theranostics. The nanomedicine concentration is a key factor to affect the theranostic efficiency and systematic toxicity. Herein, we unravel a concentration‐dependent subcellular distribution of near‐infrared‐emitting gold nanoparticles (AuNPs) co‐coated with glutathione and a cell‐penetrating peptide CR8 (CR‐AuNPs), which shows a strong membrane‐binding at high concentration but more endocytosis for mitochondria targeting at the low concentration region. Attributing to high content of AuI and microsecond luminescent lifetimes, these AuNPs can catalyze dissolved oxygen to generate singlet oxygen (1O2) efficiently. Combining with the concentration‐dependent subcellular distribution, the luminescent AuNPs show photocytotoxicity in the relative low concentration region. These findings facilitate the fundamental understanding of the biological behaviors and potential cytotoxicity of ultrasmall luminescent AuNPs toward future theranostics.

Concentration-Dependent Subcellular Distribution of Ultrasmall Near-Infrared-Emitting Gold Nanoparticles.

The ability to accurately control the subcellular distribution of nanomedicines provides unique advantages on understanding of cellular biology and disease theranostics. The nanomedicine concentration is a key factor to affect the theranostic efficiency and systematic toxicity. Herein, we unravel a concentration-dependent subcellular distribution of near-infrared-emitting gold nanoparticles (AuNPs) co-coated with glutathione and a cell-penetrating peptide CR8 (CR-AuNPs), which shows a strong membrane-binding at high concentration but more endocytosis for mitochondria targeting at the low concentration region. Attributing to high content of AuI and microsecond luminescent lifetimes, these AuNPs can catalyze dissolved oxygen to generate singlet oxygen (1 O2 ) efficiently. Combining with the concentration-dependent subcellular distribution, the luminescent AuNPs show photocytotoxicity in the relative low concentration region. These findings facilitate the fundamental understanding of the biological behaviors and potential cytotoxicity of ultrasmall luminescent AuNPs toward future theranostics.

Core/shell structural ultra-small gold and amyloid peptide nanocomposites with effective bacterial surface adherence and enhanced antibacterial photothermal ablation

The exploration of ultra-small gold nanoparticles (Au NPs) (<5 ​nm) based photothermal nanoagent is important for antibacterial photothermal therapy due to their high biosafety. However, the ultra-small Au NPs usually have low absorption in near infrared (NIR) region, presenting poor NIR-based photothermal conversion. In the present work, a novel core/shell structural gold and amyloid peptide Aβ25-35 nanocomposites (Au@Aβ NCs) were constructed with ultra-small Au NPs (ca. 4.0 ​nm) as the core and Aβ25-35 oligomer as the shell (ca. 3 ​nm thickness) through the facile peptide templated chemical reduction method. The Au@Aβ NCs display enhanced NIR absorption and photothermal conversion efficiency as compared to pure Au NPs due to the extinction of Aβ shell. In addition, the Au@Aβ NCs can strongly adhere to the bacterial surfaces and aggregate together by virtue of the intrinsic self-assembly property of amyloid peptide, which facilitates the local photothermal ablation of bacteria. Consequently, the Au@Aβ NCs can fast and completely kill the pathogenic bacteria under NIR laser irradiation. This work provides an alternative strategy to prepare highly efficient ultra-small Au NPs based photothermal nanoagent for enhancing the antibacterial photothermal ablation.

Beyond gold nanoparticles cytotoxicity: Potential to impair metastasis hallmarks

Gold nanoparticle (AuNP)-based systems have been extensively investigated as diagnostic and therapeutic agents due to their tunable properties and easy surface functionalization. Upon cell uptake, AuNPs present an inherent cell impairment potential based on organelle and macromolecules damage, leading to cell death. Such cytotoxicity is concentration-dependent and completely undesirable, especially if unspecific. However, under non-cytotoxic concentrations, internalized AuNPs could potentially weaken cells and act as antitumor agents. Therefore, this study aimed to investigate the antitumor effect of ultrasmall AuNPs (~3 nm) stabilized by the anionic polysaccharide gum arabic (GA-AuNPs). Other than intrinsic cytotoxicity, the focus was downregulation of cancer hallmarks of aggressive tumors, using a highly metastatic model of melanoma. We first demonstrated that GA-AuNPs showed excellent stability under biological environment. Non-cytotoxic concentrations to seven different cell lines, including tumorigenic and non-tumorigenic cells, were determined by standard 2D in vitro assays. Gold concentrations ≤ 2.4 mg L−1 (16.5 nM AuNPs) were non-cytotoxic and therefore chosen for further analyses. Cells exposed to GA-AuNPs were uptaken by melanoma cells through endocytic processes. Next we described remarkable biological properties using non-cytotoxic concentrations of this nanomaterial. Invasion through an extracellular matrix barrier as well as 3D growth capacity (anchorage-independent colony formation and spheroids growth) were negatively affected by 2.4 mg L−1 GA-AuNPs. Additionally, exposed spheroids showed morphological changes, suggesting that GA-AuNPs could penetrate into the preformed tumor and affect its integrity. All together these results demonstrate that side effects, such as cytotoxicity, can be avoided by choosing the right concentration, nevertheless, preserving desirable effects such as modulation of key tumor cell malignancy features.

Strict DNA Valence Control in Ultrasmall Thiolate-Protected Near-Infrared-Emitting Gold Nanoparticles.

Realizing robust DNA functionalization with strict valence control in the sub-2-nm thiolate-protected luminescent gold nanoparticles (AuNPs) is highly demanded but remains unsolved due to their unique Au(0) core and Au(I)-S shell structures. Herein, we report a facile strategy using phosphorothioates (ps)-modified DNA (psDNA) as a template for in situ growth of near-infrared (NIR)-emitting AuNPs with precisely controlled DNA valence. In addition, the particle size could be finely tuned in ultrasmall ranges from 1.3 to 2.6 nm with regulation of the ps length of psDNA. The ultrasmall NIR-emitting AuNPs bearing strict DNA valence are also demonstrated to be as powerful building block for well-organized one-dimensional assembly and optical probe for targeted cellular imaging. Such a facile strategy in decoration of luminescent AuNPs with strict DNA valence provides a new pathway for development of surface-functionalizable ultrasmall metal nanoplatforms toward various downstream applications.