Functionalized Gold Nanorods Research Articles

Single-particle rotational sensing for analyzing the neutralization activity of antiviral antibodies

Due to the pathogen-specific targeting, neutralization capabilities, and enduring efficacy, neutralizing antibodies (NAs) have received widespread attentions as a critical immunotherapeutic strategy against infectious viruses. However, because of the high variability and complexity of pathogens, rapid determination of neutralization activity of antiviral antibodies remains a challenge. Here, we report a new method, named as out-of-plane polarization imaging based single-particle rotational sensing, for rapid analysis of neutralization activity of antiviral antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the spike protein functionalized gold nanorods (AuNRs) and angiotensin-converting enzyme 2 (ACE2) coated gold nanoparticles (AuNPs) as the rotational sensors and chaperone probes, we demonstrated the single-particle rotational sensing strategy for the measurement of rotational diffusion coefficient of the chaperone-bound rotational sensors caused by the specific spike protein-ACE2 interactions. This enables us to measure the neutralizing activity of neutralizing antibody from the analysis of dose-dependent changes in rotational diffusion coefficient (Dr) of the rotational sensors upon the treatment of SARS-CoV-2 antibody. With this technique, we achieved the quantitative determination of neutralization activity of a commercially available SARS-CoV-2 antibody (IC50, 294.1 ng/mL) with satisfying accuracy and anti-interference ability. This simple and robust method holds the potential for rapid and accurate evaluation of neutralization activity against different pathogenic viruses.

An oleanic acid decorated gold nanorod for highly efficient inhibition of hemagglutinin and visible rapid detection of the influenza virus

Accurate diagnosis and effective antiviral treatments are urgently needed for the prevention and control of flu caused by influenza viruses. In this study, a novel oleanic acid (OA) functionalized gold nanorod OA-AuNP was prepared through a convenient ligand-exchange reaction. As hemagglutinin (HA) on the viral surface binds strongly to the multiple OA molecules on the surface of the nanoparticle, the prepared OA-AuNP was found to exhibit potent antiviral activity against a wide range of influenza A virus strains. Furthermore, the change in color resulting from the specific binding between HA and OA and the resultant aggregation of the OA-AuNP can be visually observed or measured by UV–vis spectra with a detection limit of 2 and 0.18 hemagglutination units (HAU), respectively, which is comparable to the commercially available influenza colloid gold rapid diagnostic kits. These findings demonstrate the potential of the OA-AuNP for the development of novel multivalent antiviral conjugates and the diagnosis of influenza virus.

Enhanced catalytic activity of tannic acid functionalized gold nanorods toward the reduction of 4-nitrophenol

The conversion of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) with sodium borohydride (NaBH4) is the most used chemical reaction for investigating the catalytic activity of various nanomaterials by ultraviolet–visible (UV–Vis) absorption spectroscopy. Herein, a simple approach is reported for the preparation of tannic acid-functionalized gold nanorods (TA-AuNRs), which functioned as catalysts for the reduction of 4-NP with NaBH4. Various processes including UV–Vis absorption spectroscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential, and X-ray photoelectron spectroscopy were employed to characterize the TA-AuNRs. They exhibited good catalytic activity during the conversion of 4-NP. Under optimal conditions, the conversion efficiency was up to 79.04% in 20 min. The reduction reaction followed the pseudo-first-order kinetics, and the rate constant was estimated to be 0.0827 min−1. The active species responsible for the conversion efficiency were investigated through scavenger experiments using 1,4-benzoquinone, isopropyl alcohol (IPA), and ammonia oxalate as scavengers. The conversion efficiency decreased to 35.74% in the presence of IPA, indicating that hydroxyl radicals were the main species that degraded 4-NP. Finally, five recycling steps confirmed the reusability and practical application potential of the TA-AuNRs for the catalytic reduction of water samples spiked with 4-NP.

Functionalized gold nanorods turn-on chemosensor for selective detection of Cd2+ ions, bio-imaging, and antineoplastic evaluations

A colorimetric turn-on chemosensor based on gold nanorods, Au NRs, has been developed to enable rapid, facile, and simultaneous detection of hazardous metal ions. This study involved the functionalization of gold nanorods with (9,10-dioxo-9,10-dihydro-anthracen-1-yl)-dithiocarbamic acid (DTAD) through the utilization of synthetic photo-irradiation and ultrasound techniques. Various spectroscopic methods were employed to characterize both the synthesized gold nanorods and the chemosensor. The optical response of this sensor was investigated with respect to a range of metal ions, including Mg2+, K+, Ca2+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+. The results reveal that the DTAD-functionalized gold nanorods chemosensor effectively discriminates all the investigated metal ions, with Cd2+ ions exhibiting higher sensitivity and selectivity compared to the other metal ions. Moreover, the anticancer impact of both gold nanorods and DTAD-functionalized gold nanorods was investigated on a panel of cell lines as breast cancer (MCF-7), liver cancer (HepG-2), and colon cancer (Caco-2) using MTT assay. Further, the morphological features and Annexin V using flow cytometry were carried. Comparative analysis with a free chemosensor showed that fluorescence images of living cells were notably brighter in the presence of Cd2+, highlighting the efficacy of DTAD-functionalized gold nanorods as a fluorescent biosensor for Cd2+ ions. Additionally, the in vitro anticancer study showed that gold nanorods significantly inhibited the growth of all cancer cells than DTAD-functionalized gold nanorods with best antiproliferative effect on HepG-2 hepatocellular carcinoma with IC50 values equal to 1.971 ± 1.28, 40.95 ± 2.56 µg/mL, respectively, compared to DOX. Also, the alteration in the HepG-2 morphological shape and Annexin V results confirmed the great antineoplastic effect of Au NRs than DTAD-Au NRs.

Development of an Antiswelling Hydrogel System Incorporating M2-Exosomes and Photothermal Effect for Diabetic Wound Healing.

Diabetic wounds represent a persistent global health challenge with a substantial impact on patients' health and overall well-being. Herein, a hydrogel system that integrates functionalized gold nanorods (AuNRs) and M2 macrophage-derived exosomes (M2-Exos) was developed to achieve an efficient and synergistic therapy for diabetic wounds. We introduced an ion-cross-linked dissipative network into a prefabricated covalent cross-linked network (long-chain polymer network), which was prepared using AuNRs as a specific cross-linker. The ion network was then cross-linked with the long-chain polymer in situ to form a specific network structure, imparting antiswelling and photothermal effects to the hydrogel. This integrated hydrogel system effectively scavenged reactive oxygen species levels, inhibited inflammation, promoted angiogenesis, and stimulated photothermal antibacterial activity through near-infrared (NIR) irradiation. To demonstrate the potential of the hydrogel, we established experimental animal models of oral mucosa ulceration and full-thickness skin defects. In vivo results confirmed that M2-Exos released from the hydrogels played a crucial role in wound closure. Furthermore, the synergistic effect of AuNRs and NIR photothermal effects eradicated bacterial infections in the wound area. Overall, our integrated hydrogel system is a promising tool for accelerating chronic diabetic wound healing and tissue regeneration. This study highlights the potential benefits of combining bioactive M2-Exos and the photothermal effect of AuNRs into an antiswelling hydrogel platform to achieve satisfactory wound healing in patients with diabetes.

Functionalized gold nanorods as drug carriers: a promising antiviral system

Functionalized gold nanorods (AuNRs) are innovative tools useful in theranostics, combining diagnostics and therapy and allowing optimal and personal treatment of patients. Moreover, AuNRs are studied for use in photothermal therapy and imaging thanks to the peculiar phenomenon of Localised Surface Plasmon Resonance (LSPR), which allows them to be identified through spectroscopic techniques in the energy range in which biological tissues are not active. Their functionalization can involve a variety of molecules, including specific drugs or peptides, allowing a controlled transport and release of desired drugs. In this framework, AuNRs were synthesised and characterised through spectroscopic (UV–Vis-NIR, XPS) and microscopic techniques (TEM, FE-SEM). Furthermore, their cytotoxic activity was evaluated on Vero E6 cell line by MTT assay. The data obtained confirm the AuNRs are promising carriers for antiviral drugs, opening new possibilities of application for biomedical field.

Active Enrichment of Nanoparticles for Ultra-Trace Point-of-Care COVID-19 Detection.

Active enrichment can detect nucleic acid at ultra-low concentrations without relatively time-consuming polymerase chain reaction (PCR), which is an important development direction for future rapid nucleic acid detection. Here, we reported an integrated active enrichment platform for direct hand-held detection of nucleic acid of COVID-19 in nanoliter samples without PCR. The platform consists of a capillary-assisted liquid-carrying system for sampling, integrated circuit system for ultrasound output, and cell-phone-based surface-enhanced Raman scattering (SERS) system. Considering the acoustic responsiveness and SERS-enhanced performance, gold nanorods were selected for biomedical applications. Functionalized gold nanorods can effectively capture and enrich biomarkers under ultrasonic aggregation. Such approaches can actively assemble gold nanorods in 1-2 s and achieved highly sensitive (6.15 × 10-13 M) SERS detection of COVID-19 biomarkers in nanoliter (10-7 L) samples within 5 min. We further demonstrated the high stability, repeatability, and selectivity of the platform, and validated its potential for the detection of throat swab samples. This simple, portable, and ultra-trace integrated active enrichment detection platform is a promising diagnostic tool for the direct and rapid detection of COVID-19.

Development of a liquid-based cytology method for detecting cervical cancer cells using functional gold nanorods

Development of a liquid-based cytology method for detecting cervical cancer cells using functional gold nanorods

Influence of Functionalized Gold Nanorods on the Structure of Cytochrome –C: An Effective Bio-nanoconjugate for Biomedical Applications

• Synthesis of gold nanoparticle (AuNPs) via wet chemical method. • Sphere shape of AuNPs was transformed to Rod shape after the 11-mercaptoundecanoic acid functionalization (11-MUA-AuNRs) • Higher colloidal stability of 11-MUA-AuNRs. • 11-MUA-AuNRs interact with Cytochrome C through electrostatic interaction. • Secondary structure of Cytochrome C was preserved in the presence of 11-MUA-AuNRs. Protein interact with functionalized nanoparticle surface (bio-nanoconjugate) has been attracted attention in various biomedical applications such as biosensing, bioimaging, tissue engineering and drug delivery etc. However, the formation of bio-nanoconjugate is inadequately understood in various biomedical applications due to their complex structures. Hence, there is an urgent need to understand the formation of bio-nanoconjugate for safe nanobiomedicine. In this study, we have prepared 11-mercaptoundecanoic acid (11-MUA) functionalized gold nanorods (AuNRs, length 30nm x width 8 nm) with aspect ratio of 3.75 ± 0.10 through wet chemical method. Optical property, size, morphology, colloidal stability of functionalized gold nanorods (Au-11-MUANRs) were characterized through UV-visible, HR-TEM, DLS, Zeta potential and FT-IR spectral techniques. These functionalized gold nanorods with various concentrations were interacted with Cytochrome C (Cyt-C) under the similar physiological condition (pH 7.4) and its subsequent structural changes were examined through Circular dichroism spectroscopy. The obtained CD result indicated that Au-11-MUANRs were slightly altering the structural conformation of Cyt-C at higher concentration due to the stronger electrostatic interaction between the positively charged Cyt-C with negatively charged Au-11-MUANRs. This study clearly reveals that lower concentration (< 1µM) of Au-11-MUANRs interacted Cyt-C based nanobio-conjugate as potential material for safe biomedical applications.

Shiga Toxin-B Targeted Gold Nanorods for Local Photothermal Treatment in Oral Cancer Clinical Samples.

A great challenge in nanomedicine, and more specifically in theranostics, is to improve the specificity, selectivity, and targeting of nanomaterials towards target tissues or cells. The topical use of nanomedicines as adjuvants to systemic chemotherapy can significantly improve the survival of patients affected by localized carcinomas, reducing the side effects of traditional drugs and preventing local recurrences. Here, we have used the Shiga toxin, to design a safe, high-affinity protein-ligand (ShTxB) to bind the globotriaosylceramide receptor (GB3) that is overexpressed on the surfaces of preneoplastic and malignant cancer cells in the head and neck tumors. We find that ShTxB functionalized gold nanorods are efficiently retrotranslocated to the GB3-positive cell cytoplasms. After 3 minutes of laser radiation with a wavelength resonant with the AuNR longitudinal localized surface plasmon, the death of the targeted cancer cells is activated. Both preclinical murine models and patient biopsy cells show the non-cytotoxic nature of these functionalized nanoparticles before light activation and their treatment selectivity. These results show how the use of nanomedicines directed by natural ligands can represent an effective treatment for aggressive localized cancers, such as squamous cell carcinoma of the oral cavity.

Antimicrobial peptide functionalized gold nanorods combining near-infrared photothermal therapy for effective wound healing

Photothermal therapy using laser activated gold nanorods (AuNRs) is a strategy for treatment of bacterial infections. Nevertheless, it also exerts cytotoxicity against human cells which leads to adverse effects in healthy human tissues and limits the applicable dose. Functionalization of AuNRs with a selective antimicrobial peptide (AMP) with higher selectivity for bacteria over human cells is a promising strategy for increasing the selectivity of the AuNRs for bacteria, hence increasing their cellular uptake by the bacteria in order to achieve stronger antimicrobial effects with lower doses of AuNRs without damaging the human cells. In this study, the surface of AuNRs was functionalized with a short AMP named C-At5 and the efficiency of the peptide functionalized AuNRs in killing gram-positive and gram-negative bacteria was evaluated in vitro as well as their potential for facilitating wound healing in a mouse model of wound infection with and without application of laser. The peptide-conjugated AuNRs exhibited higher antibacterial activity in vitro compared to the plain AuNRs both in the presence and absence of laser irradiation. Furthermore, AuNR@C-At5 had very low toxicity against human skin fibroblasts and human red blood cells indicating their higher biocompatibility compared to the plain AuNRs. Treatment of wounded mice with AuNR@C-At5 accelerated the wound healing process which was further enhanced by applying laser. The system developed in this study has great potential for customization for specific antimicrobial or antifungal therapy via conjugation of different types of AMPs with higher selectivity and can therefore serve as a guide for any future attempts in this regard.

Neuropeptide-Functionalized Gold Nanorod Enhanced Cellular Uptake and Improved In Vitro Photothermal Killing in LRP1-Positive Glioma Cells.

The therapeutic modalities for glioblastoma multiforme fail badly due to the limitations of poor penetration through the blood–brain barrier and the lack of tumor targeting. In this study, we synthesized a neuropeptide (ANGIOPEP-2)-functionalized gold nanorod (GNR-ANGI-2) and systemically evaluated the cellular uptake and photothermal effects enhanced by the neuropeptide functionalization of the gold nanorod under laser or sham exposure. The expression of LRP1, the specific ligand for ANGIOPEP-2, was the highest in C6 cells among five studied glioma cell lines. The cellular internalization studies showed higher uptake of gold nanorods functionalized with ANGIOPEP-2 than of those functionalized with scrambled ANGIOPEP-2. The in vitro photothermal studies of C6 cells treated with GNR-ANGI-2 and laser showed a higher rate of apoptosis at early and late stages than cells treated with GNR-ANGI-2 without laser. Correspondingly, in vitro ROS evaluation showed a higher intensity of ROS production in cells treated with GNR-ANGI-2 under laser irradiation. The Western blotting results indicated that GNR-ANGI-2 with laser exposure activated the caspase pathway of apoptosis, and GNR-ANGI-2 with sham exposure induced autophagy in C6 cells. The current study provides in-depth knowledge on the effective time point for maximum cellular uptake of GNR-ANGI-2 to achieve a better anti-glioma effect. Moreover, by exploring the molecular mechanism of cell death with GNR-ANGI-2-mediated photothermal therapy, we could modify the nanoshuttle with multimodal targets to achieve more efficient anti-glioma therapy in the future.

Design and Fabrication of pH-Sensitive Curcumin Coated Gold Nanorods as Anti-Angiogenic Targeting Nanostructures

Curcumin's limited bioavailability, caused by its hydrophobic nature, is a significant stumbling block to its application. This paper describes the development of a pH-responsive targetable carrier that overcomes the challenges associated with using curcumin. The use of gold nanorods in the creation of curcumin nanocarriers aids the combination of plasmonic phototherapy with biotherapy. This study used the pH-sensitive release and receptor targeting nanocarriers poly-L-histidine and ATWLPPR. The carrier's components are confirmed through synthesis and characterization. At a concentration of 0.66 g/mL), the functionalized gold nanorod nanocarrier had a 32 - 43 nm size range. The gold nanorod level is increased to 1.33 g/mL by crosslinking them with amine-functionalized PEG. Curcumin was released in a pH-dependent manner by the nanocarrier. Furthermore, in vitro tests to corroborate the efficiency of this therapeutic model show that when gold nanorods are routed through the peptide, the intake of gold nanorods is doubled.

Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates

The β-amyloid (Aβ) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of Aβ species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of Aβ in animal models in the near-infrared region (NIR). However, considering future applications in biomedicine, it is relevant to develop strategies to improve detection of amyloid aggregates using NIR probes. An innovative approach to increase the fluorescence signal of these fluorophores is the use of plasmonic gold nanoparticles (surface-enhanced fluorescence effect). In this work, we improved the detection of Aβ aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods (GNRs-PEG-D1) with the fluorescent probes CRANAD-2 or CRANAD-58, which bind selectively to different amyloid species (soluble and insoluble). This work shows that GNRs improve the detection of Aβ using NIR probes in vivo.

An ultrasensitive biosensor for prostate specific antigen detection in complex serum based on functional signal amplifier and designed peptides with both antifouling and recognizing capabilities

The development of biosensors capable of averting biofouling and detecting biomarkers in complex biological media remains a challenge. Herein, an ultralow fouling and highly sensitive biosensor based on specifically designed antifouling peptides and a signal amplification strategy was designed for prostate specific antigen (PSA) detection in human serum. A low fouling layer of poly(ethylene glycol) (PEG) doped the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrodeposited on the electrode surface, followed by the immobilization of streptavidin and further attachment of biotin-labelled peptides. The peptide was designed to include PSA specific recognition domain (HSSKLQK) and antifouling domain (PPPPEKEKEKE), and the terminal of the peptide was functionalized with –SH group. DNA functionalized gold nanorods (DNA/AuNRs) were then attached to the electrode, and methylene blue (MB) molecules were adsorbed to the DNA to form the signal amplifier. In the presence of PSA, the peptide was specifically cleaved and resulted in the loss of AuNRs together with DNA and MB, and thus significant decrease of the current signal. The biosensor exhibited a low limit of detection (LOD) of 0.035 pg mL-1 (S/N = 3), with a wide linear range from 0.10 pg mL-1 to 10.0 ng mL-1, and it was able to detect PSA in real human serum owing to the presence of the antifouling peptides, indicating great potential of the constructed biosensor for practical application.

Delivery of siRNA Using Functionalized Gold Nanorods Enhances Anti-Osteosarcoma Efficacy.

Gold nanorods (GNRs) are intensively explored for the application in cancer therapy, which has motivated the development of photothermal therapy (PTT) multifunctional nanoplatforms based on GNRs to cure osteosarcoma (OS). However, the major limitations include the toxicity of surface protectants of GNRs, unsatisfactory targeting therapy, and the resistant effects of photothermal-induced autophagy, so the risk of relapse and metastasis of OS increase. In the present study, the GNR multifunctional nanoplatforms were designed and synthesized to deliver transcription factor EB (TFEB)-siRNA–targeting autophagy; then, the resistance of autophagy to PTT and the pH-sensitive cell-penetrating membrane peptide (CPP) was weakened, which could improve the tumor-targeting ability of the GNR nanoplatforms and realize an efficient synergistic effect for tumor treatment. Meanwhile, it is worth noting that the GNR nanoplatform groups have anti-lung metastasis of OS. This study provides a new reference to improve the efficacy of OS clinically.

Plasmonic Amyloid Tactoids (Adv. Mater. 51/2021)

Liquid-Crystalline Droplets In article number 2106155, Raffaele Mezzenga and co-workers demonstrate a schematic representation of amyloid fibrils confined within a liquid-crystalline droplet formed by liquid–liquid-crystalline phase separation, and organized in a chiral nematic conformation, capable of guiding the spatial and orientational distribution of functionalized gold nanorods added to the colloidal system.

Altering model cell membranes by means of photoactivated organic functionalized gold nanorods

A possible non-invasive photothermal therapy employs photothermal agents with high light-to-heat conversion efficiency. Gold nanorods (Au-NRs) can be applied as photothermal agents because of their optical properties and specific tumor-targeting capability. The potential therapeutic applications and toxicological effects of photothermal agents depend on the interaction of the Au-NRs with the cell membrane, the understanding of which is of great importance. Although studies in this area have been performed, the interactions between model cell membranes and photoactivated Au-NRs have not yet been described. In this study, we explain how local excitation of the Au-NRs caused a local temperature increase in their vicinity that affected the properties of a model membrane composed of dipalmitoylphosphatidylcholine (DPPC). Our results showed that the illumination of the Au-NRs changed the DPPC’s organization in the Langmuir monolayer. Upon photoactivation, the mutual distances between the DPPC molecules increased; however, the conformation of the lipid tails remained unchanged. Moreover, the illumination of the membrane at a surface pressure corresponding to that in a native cellular membrane caused a more stable and elastic behavior of the Langmuir monolayer. The results obtained corroborate the theory that photoactivation of Au-NRs influences the packing and phase behavior of mimetic cell membranes. In the long term, it may allow us to understand how the photoactivation of nanoparticles facilitates the transport of medicinal substances.

Multiplexed detection of heavy metal ions by single plasmonic nanosensors

Detection of multiple analytes simultaneously in small liquid samples with high efficiency and precision is highly important to the fields like water quality monitoring. In this letter, we present a multiplexed nanosensors with position-encoded aptamer functionalized gold nanorods for heavy metal ions detection. The individual gold nanorods respond specifically to two different heavy metal ions (Pb2+ and Hg2+) with a spectral shift in the scattering spectrum. We used a home-built spectral imaging dark-field microscope to measure the response of thousands of single plasmonic nanosensors with relatively high time resolution and precision. To explore the performance and limit of detection (LOD) of our nanosensor and setup, we recorded the concentration-dependent response of our position-encoded nanosensors with a series of mixture solutions that contain different concentrations of Hg2+ and Pb2+ ions. The LOD levels of our system are around 5 nM for Pb2+ ions and 1 nM for Hg2+ ions. Our method and results demostrate the nanomolar sensitivity and the potential to detect more different heavy metal ions.

Functionalized Gold Nanorod Probes: A Sophisticated Design of SERS Immunoassay for Biodetection in Complex Media.

Surface-enhanced Raman scattering (SERS) probes offer considerable opportunities in label-based biosensing and analysis. However, achieving specific and reproducible performance, where low detection limits are needed in complex media, remains a challenge. Herein, we present a general strategy employing gold nanorod SERS probes and rationally designed surface chemistry involving protein resistant layers and antibodies to allow for the selective detection of species in complex media. By utilizing the ability of gold nanorods for selective surface modification, Raman reporters (4-mercaptobenzoic acid) were attached to the tips. Importantly, the sides of the nanorods were modified using a mixed layer of two different length stabilizing ligands (carboxyl-terminated oligo ethylene glycols) to ensure colloidal stability, while antibodies were attached to the stabilizing ligands. The nanoparticle interfacial design improves the colloidal stability, unlocks the capability of the probes for targeting biomolecules in complex matrices, and gives the probes the high SERS efficiency. The utility of this probe is demonstrated herein via the detection of Salmonella bacteria at the single bacterium level in complex food matrices using an anti-Salmonella IgG antibody-conjugated probe. The modular nature of the surface chemistry enables the SERS probes to be employed with a molecularly diverse range of biorecognition species (e.g., antibodies and peptides) for many different analytes, thus opening up new opportunities for efficient biosensing applications.