Multifunctional Gold Nanoparticles Research Articles

Multifunctional gold nanoparticles for cancer theranostics.

The diagnosis and treatment of cancer can often be challenging requiring more attractive options. Some types of cancers are more aggressive than others and symptoms for many cancers are subtle, especially in the early stages. Nanotechnology provides high sensitivity, specificity and multimodal capability for cancer detection, treatment and monitoring. In particular, metal nanoparticles (NPs) such as gold nanoparticles (AuNPs) are attractive nanosystems for researchers interested in bioimaging and therapy. The size, shape and surface of AuNPs can be modified for improving targeting and accumulation in cancer cells, for example through introduction of ligands and surface charge. The interactions of AuNPs with electromagnetic radiation (e.g., visible-near-infrared, X-rays) can be used for photothermal therapy and radiation therapy, through heat generated from light absorption and emission of Auger electrons, respectively. The subsequent expansion and high X-ray attenuation from AuNPs can be used for enhancing contrast for tumor detection (e.g., using photoacoustic, computed tomography imaging). Multi-functionality can be further extended through covalent/non-covalent functionalization, for loading additional imaging/therapeutic molecules for combination therapy and multimodal imaging. In order to cover the important aspects for designing and using AuNPs for cancer theranostics, this review focuses on the synthesis, functionalization and characterization methods that are important for AuNPs, and presents their unique properties and different applications in cancer theranostics.

Development of multifunctional H2S-releasing gold nanoparticles for chronic wound treatment

Chronic wounds, characterized by prolonged inflammation, require new therapies to improve healing. Hydrogen sulfide (H2S), a key neurotransmitter, supports critical factors in wound healing but is often deficient in chronic wounds. Despite its potential, the toxicity of direct H2S delivery and the unsustainable release from current systems hinder its therapeutic use. This study introduces H2S-releasing gold nanoparticles synthesized by reducing chloroauric acid (HAuCl4) with diallyl trisulfides (DATS), a naturally derived H2S donor. These nanoparticles are hypothesized to be biocompatible and multifunctional, combining H2S release with the beneficial properties of gold. Results show that DATS does not impair H2S release, and higher DATS concentrations enhance H2S output. The sustained H2S release promotes endothelial cell proliferation, migration, and angiogenesis while retaining the antimicrobial properties of gold nanoparticles, making this material promising for chronic wound treatment.

Insights into the Engineered Gold Nanoparticle-Based Remedy for Supplementation Therapy of Ovarian Carcinoma.

Chronic diseases, notably cancer, pose a significant global threat to human life. Oncologists and medical professionals addressing malignancies confront challenges such as toxicity and multidrug resistance. To tackle these issues, the focus has shifted toward the employment of multifunctional colloidal gold nanoparticles. This study aims to design pH-sensitive doxorubicin-loaded gold nanoparticles using polyvinylpyrrolidone. The cytotoxic efficacy of the designed gold nanoarchitecture and its doxorubicin counterpart was assessed in an in vitro model using the HeLa cell. In comparison to the free drug, experimental evaluations showed that the gold nanoarchitecture outperformed significantly lower unspecific drug leaching and efficiently delivered the payload in a controlled manner, boosting the chemotherapy outcomes. This work opens a streamlined approach for engineering gold nanoarchitecture that could be further expanded to incorporate other therapeutics and/or functional moieties that require optimized controlled delivery, offering a one-size-fits-all solution and paving the revolutionary adjustments to healthcare procedures.

Synthesis of multifunctional silver oxide, zinc oxide, copper oxide and gold nanoparticles for enhanced antibacterial activity against ESKAPE pathogens and antioxidant, anticancer activities using Momordica cymbalaria seed extract

Rising emergence in public health due to antibiotic-resistant of ESKAPE pathogens, diseases related to oxidative damage and cancer has driven the urgent need to develop potent therapeutics for resistant bacterial strains, free radical scavenging and cancer. The present study involves Momordica cymbalaria seed extracts mediated synthesis of metal nanoparticles and to evaluate its ameliorative potency against ESKAPE pathogens, free radicals and cancer cells. The study includes therapeutic approaches to target pathogenic biofilms relating phyto-therapeutics with nanotechnology. In the present investigation, we have synthesized four metal oxide nanoparticles of Silver, Zinc, Copper (Ag2O, ZnO and CuO), and Gold nanoparticles (Au NPs) using the seed extracts of M. cymbalaria. The synthesized nanoparticles were characterized by various biophysical techniques like X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) Field-Emission Scanning Electron Microscopy (FESEM) with energy-dispersive X-ray spectroscopy (EDX) and High-Resolution Transmission Electron Microscopy (HR-TEM) with Selected Area Electron Diffraction (SAED). Agar well diffusion methods, or Antimicrobial methods (MIC, MBC, and MBIC), DPPH/ABTS free radical scavenging assay, MTT/apoptotic studies and protein/DNA damage inhibition assays were performed to evaluate the antibacterial, anticancer and antioxidant activities. Crystalline properties of metal oxides NPs were established by XRD pattern and the presence of alcohol or phenol, ketone, and amine groups in M. cymbalaria seed was confirmed by FTIR analysis. That participates in the reduction of Ag+, Cu+, Zn+, and Au+ ions to NPs. All the nanoparticles showed dose-dependent antibacterial, anticancer and antioxidant activity. Protein and DNA oxidation inhibition assays demonstrated an efficient quenching effect of proxy radicals by all the NPs. Therefore, M. cymbalaria -mediated synthesis of metal NPs can be used as an alternative to toxic physical or chemically mediated synthesis that can be applied to develop multifunctional nanoparticles as efficient therapeutics.

Thespesia lampas mediated green synthesis of silver and gold nanoparticles for enhanced biological applications

The present study investigated the synthesis and biological applications of green, economical, and multifunctional silver and gold nanoparticles (TSAgNPs and TSAuNPs) using the ethnomedical important medicinal plant Thespesia lampas for biological activities. Relatively higher levels of antioxidant components were measured in T. lampas compared to the well-known Adhatoda vasica, and Diplocyclos palmatus suggested the potential of T. lampas for the study. Synthesized TSAgNPs and TSAuNPs were characterized through UV-Vis, XRD, SEM-EDS, HR-TEM, SAED, and FTIR techniques. SEM revealed that TSAgNPs and TSAuNPs were predominantly spherical in shape with 19 ± 7.3 and 43 ± 6.3 nm crystal sizes. The sizes of TSAgNPs and TSAuNPs were found to be12 ± 4.8 and 45 ± 2.9 nm, respectively, according to TEM measurements. The FTIR and phytochemical analyses revealed that the polyphenols and proteins present in T. lampas may act as bio-reducing and stabilizing agents for the synthesis. Synthesized NPs exhibited enhanced scavenging properties for ABTS and DPPH radicals. TSAgNPs and TSAuNPs were able to protect DNA nicking up to 13.48% and 15.38%, respectively, from oxidative stress. TSAgNPs possessed efficient antibacterial activities in a concentration-dependent manner against human pathogenic bacteria, such as E. coli, B. subtilis, P. vulgaris, and S. typhi. Furthermore, TSAgNPs and TSAuNPs showed significant cytotoxicity against FaDu HNSCC grown in 2D at 50 and 100 μg mL-1. Tumor inhibitory effects on FaDu-derived spheroid were significant for TSAgNPs > TSAuNPs at 100 μg mL-1 in 3D conditions. Dead cells were highest largely for TSAgNPs (76.65% ± 1.76%), while TSAuNPs were non-significant, and Saq was ineffectively compared with the control. However, the diameter of the spheroid drastically reduced for TSAgNPs (3.94 folds) followed by TSAuNPs (2.58 folds), Saq (1.94 folds), and cisplatin (1.83 folds) at 100 μg mL-1. The findings of the study suggested the bio-competence of TSAgNPs and TSAuNPs as multi-responsive agents for antioxidants, DNA protection, antibacterial, and anti-tumor activities to provide a better comprehension of the role of phytogenic nanoparticles in healthcare systems.

Ferromagnetic resonance-based heat dissipation in dumbbell-like Au–Fe3O4 nanoparticles

Ferromagnetic resonance (FMR) holds promise for heating magnetic nanoparticles (MNPs) in cancer therapy, especially for rapidly heating MNPs. This study aims to enhance the FMR-based heating efficiency of multifunctional hybrid gold and iron oxide nanoparticles (Au-Fe3O4 NPs) as theranostic agents. We experimentally investigate the FMR-based heating properties of newly developed dumbbell-like Au-Fe3O4 NPs, which feature ∼5 nm gold and 15 nm iron oxide components, in comparison to our previously developed Au-coated Fe3O4 NPs (Fe3O4 core ∼5.2 nm, Au shell thickness ∼0.5 nm). For comparison, we also synthesize pure Fe3O4 NPs (∼11 nm) under the same experimental conditions as the dumbbell-like Au-Fe3O4 NPs but without 5 nm Au seeds. Temperature measurements are taken at various DC fields (HDC = 0‒1600 Oe) under a radiofrequency (RF) field (fAC = 4 GHz, HAC = 1.265 Oe) for ∼13s. The results reveal a rapid temperature rise during RF field ON, followed by a decline upon RF field OFF. Remarkably, dumbbell-like Au-Fe3O4 NPs achieve a peak temperature increase of 23.4 °C, corresponding to a heating rate of 1.73 °C/s at HDC = 400 Oe, surpassing the combined values of ∼11 nm Fe3O4 NPs (11.0 °C, i.e., 0.83 °C/s at HDC = 1000 Oe) and ∼5 nm Au NPs (3.5 °C). Comparing these results to our previously developed Au-coated Fe3O4 NPs, which achieved a heating rate of 1.29 °C/s (temperature rise 16.9 °C) under HDC = 1200 Oe with an RF field at fAC = 4 GHz and a significantly higher HAC = 4 Oe (i.e. for HAC = 1.265 Oe, the estimated heating rate was 0.129 °C/s with a temperature rise of 1.69 °C), the dumbbell-shaped Au-Fe3O4 NPs demonstrate a substantially higher temperature increase by 13.4 times. These findings highlight the exceptional potential of dumbbell-shaped Au-Fe3O4 NPs for application in magnetic hyperthermia.

Dual-responsive amplification strategy for ultrasensitive detection of norovirus in food samples: Combining magnetic relaxation switching and fluorescence assay

Ultra-sensitive, accurate, and specific diagnostic probes are urgently developed to overcome the limitations of conventional norovirus (NV) probes. Herein, we presented the fabrication of a dual-signal probe using multifunctionalized gold and magnetic nanoparticles hybrid composite (Fe3O4 @Au NPs) carriers for the specific detection of NV by magnetic relaxation-fluorescence bimodal sensing. The dual-specific probes were created by modifying Fe3O4 @Au NPs with antibody (Ab) and aptamer-FAM. The antigen-Ab immunoreaction caused aggregation of Fe3O4 @Au NPs, altering the magnetic relaxation signal; simultaneously, the aptamer-FAM that were originally adsorbed on the Au surface were desorbed and cleaved into the solution in the presence of NV, causing a change in the fluorescence signal. Ultrahigh detection sensitives of 0.38 and 3.45 pg/mL were obtained for the dual-modality detection platform, respectively. Furthermore, two quantitative methods obtained satisfactory spiked recoveries for NV-spiked oyster, scallop, strawberry, and tomato samples, consistent with the results of commercial ELISA kits. The results indicated that this dual-specificity assay not only was ultrasensitive but also markedly boosted analysis reliability and precision. Hence, the dual-mode biosensor exhibits high potential for NV detection in the field of food safety.

Molecular Surface Quantification of Multifunctionalized Gold Nanoparticles Using UV-Visible Absorption Spectroscopy Deconvolution.

Multifunctional gold nanoparticles (AuNPs) are of great interest, owing to their vast potential for use in many areas including sensing, imaging, delivery, and medicine. A key factor in determining the biological activity of multifunctional AuNPs is the quantification of surface conjugated molecules. There has been a lack of accurate methods to determine this for multifunctionalized AuNPs. We address this limitation by using a new method based on the deconvolution and Levenberg-Marquardt algorithm fitting of UV-visible absorption spectrum to calculate the precise concentration and number of cytochrome C (Cyt C) and zinc porphyrin (Zn Porph) bound to each multifunctional AuNP. Dynamic light scattering (DLS) and zeta potential measurements were used to confirm the functionalization of AuNPs with Cyt C and Zn Porph. Transmission electron microscopy (TEM) was used in conjunction with UV-visible absorption spectroscopy and DLS to identify the AuNP size and confirm that no aggregation had taken place after functionalization. Despite the overlapping absorption bands of Cyt C and Zn Porph, this method was able to reveal a precise concentration and number of Cyt C and Zn Porph molecules attached per AuNP. Furthermore, using this method, we were able to identify unconjugated molecules, suggesting the need for further purification of the sample. This guide provides a simple and effective method to quickly quantify molecules bound to AuNPs, giving users valuable information, especially for applications in drug delivery and biosensors.

Targeted Doxorubicin-Loaded Dendronized Gold Nanoparticles.

Dendronized nanoparticles, also called nanoparticle-cored dendrimers, combine the advantages of nanoparticles and dendrimers. These very stable and polyvalent nanoparticles can be used for diverse applications. One such application is drug delivery, because the dendrons can enhance the density of the payload. In this report, we describe the design of multifunctional gold nanoparticles (AuNPs) coated with poly(propylene imine) (PPI) dendrons that contain both prostate cancer active targeting and chemotherapeutic drugs. The PPI dendron is a good candidate for the design of drug delivery vehicles because of its ability to induce a proton sponge effect that will enhance lysosomal escape and intracellular therapeutic delivery. The chemotherapeutic drug used is doxorubicin (DOX), and it was linked to the dendron through a hydrazone acid-sensitive bond. Subsequent acidification of the AuNP system to a pH of 4-5 resulted in the release of 140 DOX drugs per nanoparticles. In addition, the PPI dendron was conjugated via "click" chemistry to an EphA2-targeting antibody fragment that has been shown to target prostate cancer cells. In vitro cell viability assays revealed an IC50 of 0.9 nM for the targeted DOX-bearing AuNPs after 48 h incubation with PC3 cells. These results are very promising upon optimization of the system.

Verification of Nanomaterial-Induced Size-Dependent Human Ether-à-Go-Go-Related Gene Potassium Channel Blockage Using Three-Dimensional Bioengineered Functional Cardiac Tissue Constructs

Three-dimensional (3D) bioprinted functional cardiac tissue constructs are proposed for the first time as a screening platform to evaluate the nanomaterial-induced hERG potassium channel blockage based on the in situ measurement of K+ permeation and hERG protein immunofluorescence. Multifunctional anticancer spherical gold nanoparticles whose surface was bound with the ligand of thiol-terminated polyethylene glycol (PEG) conjugated to indomethacin (IMC-PEG-SH@AuNPs) were synthesized with mean diameters of 19, 33, and 64 nm. Triphenylphosphine-stabilized gold nanoparticles (F-108@TPP-AuNPs) were fabricated via temperature- and reaction time-controlled synthesis. Both IMC-PEG-SH@AuNPs and F-108@TPP-AuNPs showed a dose-dependent decrease in K+ permeation because of their binding to hERG proteins. The degree of the hERG potassium channel blockage was dependent on the surface ligand conjugated to the AuNPs. The size-dependent effect of the nanomaterials on the hERG K+ channel block was quantitatively evaluated using the three different sizes of IMC-PEG-SH@AuNPs. The effect of the K+ channel block was remarkably proportional to the size of IMC-PEG-SH@AuNPs. This is the first report demonstrating the size-dependent effect of an hERG K+ channel block induced by nanomaterials. In addition, small molecules showed a greater decrease in K+ permeation and hERG immunofluorescence compared with IMC-PEG-SH@AuNPs because of steric limitations in the binding of surface ligands to hERG proteins.

Multifunctional Gold Nanoparticles in Cancer Diagnosis and Treatment.

Cancer is the second leading cause of death in the world, behind only cardiovascular diseases, and is one of the most serious diseases threatening human health nowadays. Cancer patients’ lives are being extended by the use of contemporary medical technologies, such as surgery, radiotherapy, and chemotherapy. However, these treatments are not always effective in extending cancer patients’ lives. Simultaneously, these approaches are often accompanied with a series of negative consequences, such as the occurrence of adverse effects and an increased risk of relapse. As a result, the development of a novel cancer-eradication strategy is still required. The emergence of nanomedicine as a promising technology brings a new avenue for the circumvention of limitations of conventional cancer therapies. Gold nanoparticles (AuNPs), in particular, have garnered extensive attention due to their many specific advantages, including customizable size and shape, multiple and useful physicochemical properties, and ease of functionalization. Based on these characteristics, many therapeutic and diagnostic applications of AuNPs have been exploited, particularly for malignant tumors, such as drug and nucleic acid delivery, photodynamic therapy, photothermal therapy, and X-ray-based computed tomography imaging. To leverage the potential of AuNPs, these applications demand a comprehensive and in-depth overview. As a result, we discussed current achievements in AuNPs in anticancer applications in a more methodical manner in this review. Also addressed in depth are the present status of clinical trials, as well as the difficulties that may be encountered when translating some basic findings into the clinic, in order to serve as a reference for future studies.

Multifunctional Thio-Stabilized Gold Nanoparticles for Near-Infrared Fluorescence Detection and Imaging of Activated Caspase-3.

Gold nanoparticles (AuNPs) are commonly used in nanomedicine because of their unique spectral properties, chemical and biological stability, and ability to quench the fluorescence of organic dyes attached to their surfaces. However, the utility of spherical AuNPs for activatable fluorescence sensing of molecular processes have been confined to resonance-matched fluorophores in the 500 nm to 600 nm spectral range to maximize dye fluorescence quenching efficiency. Expanding the repertoire of fluorophore systems into the NIR fluorescence regimen with emission >800 nm will facilitate the analysis of multiple biological events with high detection sensitivity. The primary goal of this study is to determine if spherical AuNP-induced radiative rate suppression of non-resonant near-infrared (NIR) fluorescent probes can serve as a versatile nanoconstruct for highly sensitive detection and imaging of activated caspase-3 in aqueous media and cancer cells. This required the development of activatable NIR fluorescence sensors of caspase-3 designed to overcome the nonspecific degradation and release of the surface coatings in aqueous media. We harnessed the fluorescence-quenching properties and multivalency of spherical AuNPs to develop AuNP-templated activatable NIR fluorescent probes to detect activated caspase-3, an intracellular reporter of early cell death. Freshly AuNPs were coated with a multifunctional NIR fluorescent dye-labeled peptide (LS422) consisting of an RGD peptide sequence that targets αvβ3-integrin protein (αvβ3) on the surface of cancer cells to mediate the uptake and internalization of the sensors in tumor cells; a DEVD peptide sequence for reporting the induction of cell death through caspase-3 mediated NIR fluorescence enhancement; and a multidentate hexacysteine sequence for enhancing self-assembly and stabilizing the multifunctional construct on AuNPs. The integrin binding affinity of LS422 and caspase-3 kinetics were determined by a radioligand competitive binding and fluorogenic peptide assays, respectively. Detection of intracellular caspase-3, cell viability, and the internalization of LS422 in cancer cells were determined by confocal NIR fluorescence spectroscopy and microscopy. Narrow size AuNPs (13 nm) were prepared and characterized by transmission electron microscopy and dynamic light scattering. When assembled on the AuNPs, the binding constant of LS422 for αvβ3 improved 11-fold from 13.2 nM to 1.2 nM. Whereas the catalytic turnover of caspase-3 by LS422-AuNPs was similar to the reference fluorogenic peptide, the binding affinity for the enzyme increased by a factor of 2. Unlike the αvβ3 positive, but caspase-3 negative breast cancer MCF-7 cells, treatment of the αvβ3 and caspase-3 positive lung cancer A549 cells with Paclitaxel showed significant fluorescence enhancement within 30 minutes, which correlated with caspase-3 specific activation of LS422-AuNPs fluorescence. Incorporation of a 3.5 mW NIR laser source into our spectrofluorometer increased the detection sensitivity by an order of magnitude (limit of detection ~0.1 nM of cypate) and significantly decreased the signal noise relative to a xenon lamp. This gain in sensitivity enabled the detection of substrate hydrolysis at a broad range of inhibitor concentrations without photobleaching the cypate dye. The multifunctional AuNPs demonstrate the use of a non-resonant quenching strategy to design activatable NIR fluorescence molecular probes. The nanoconstruct offers a selective reporting method for detecting activated caspase-3, imaging of cell viability, identifying dying cells, and visualizing the functional status of intracellular enzymes. Performing these tasks with NIR fluorescent probes creates an opportunity to translate the in vitro and cellular analysis of enzymes into in vivo interrogation of their functional status using deep tissue penetrating NIR fluorescence analytical methods.

Fabrication of a surface-enhanced Raman spectroscopy-based analytical method consisting of multifunctional DNA three-way junction-conjugated porous gold nanoparticles and Au-Te nanoworm for C-reactive protein detection.

C-Reactive protein (CRP) is a biomarker of inflammatory responses and an index for assessing the risk of cardiovascular disease and estimating prognosis. In this study, we constructed a surface-enhanced Raman spectroscopy (SERS) biosensor composed of a multifunctional DNA three-way junction (DNA 3WJ), porous gold nanoplates (pAuNPs), and an Au-Te nanoworm structure for detection of CRP. The pAuNP and Au-Te nanostructures were synthesized by galvanic replacement reactions, and the morphology was confirmed by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering (DLS). To generate the SERS signal, the Au-Te nanostructure was immobilized on an indium-tin oxide substrate, and the thiol-modified CRP aptamer was then self-assembled onto the modified substrate for CRP recognition. To amplify the SERS signal and identify the Raman tag, the multifunctional DNA 3WJ was conjugated with the pAuNPs, and each fragment of 3WJ was functionalized to biotin (pAuNP conjugation), methylene blue (Raman reporter), and CRP aptamer (target binding). The results were confirmed by gel electrophoresis. For conjugation between pAuNPs and DNA 3WJ, avidin was encapsulated in pAuNPs, and the conjugation structure was confirmed by DLS. The fabricated SERS biosensor showed detection limits of 2.23 pM in phosphate-buffered saline and 3.11 pM in diluted human serum. Overall, the proposed biosensor may have potential applications as a SERS biosensor platform.

Development of Drug Delivery Technology and Nanomedicine by Using Gold Nanoparticles

Nanomedicine is a new medical field involving the use of nanoparticles. Early examples of biocompatible nanomedicines include liposomes (Doxil®) and albumin nanoparticles (Abraxane®), and promising new nanomedicines include nanocarriers such as nanomicelles and nanoemulsions. A new trend towards the use of metal-based nanoparticles, including gold nanoparticles, has led to global clinical trials. These particles exhibit novel properties compared to conventional nanomedicines such as liposomes and albumin nanoparticles. These properties hold promise for nanomedicines, and thus the biodistribution and pharmacokinetics of metal-based nanoparticles should be carefully investigated. This had led to an increasing number of clinical trials investigating metal nanoparticles and inorganic nanoparticles. The present review evaluates multi-functional gold nanoparticles described in recent articles and shows that the unique properties of gold nanoparticles are applicable for not only drug delivery, but also for imaging. The combined therapeutic modality between therapeutics and diagnostics is called "theranostics" and is promising for future personalized cancer therapy. This review also introduces recent research from our laboratory involving the use of various kinds of molecules [polyethylene glycol (PEG), drug/cyclodextrin inclusion complexes, biosimilars and small interfering (siRNAs)] loaded onto and/or conjugated with gold nanoparticles.

Rational Design of Albumin Theranostic Conjugates for Gold Nanoparticles Anticancer Drugs: Where the Seed Meets the Soil?

Multifunctional gold nanoparticles (AuNPs) may serve as a scaffold to integrate diagnostic and therapeutic functions into one theranostic system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. Herein, albumin-AuNP theranostic agents have been obtained by conjugation of an anticancer nucleotide trifluorothymidine (TFT) or a boron-neutron capture therapy drug undecahydro-closo-dodecaborate (B12H12) to bimodal human serum albumin (HSA) followed by reacting of the albumin conjugates with AuNPs. In vitro studies have revealed a stronger cytotoxicity by the AuNPs decorated with the TFT-tagged bimodal HSA than by the boronated albumin conjugates. Despite long circulation time, lack of the significant accumulation in the tumor was observed for the AuNP theranostic conjugates. Our unique labelling strategy allows for monitoring of spatial distribution of the AuNPs theranostic in vivo in real time with high sensitivity, thus reducing the number of animals required for testing and optimizing new nanosystems as chemotherapeutic agents and boron-neutron capture therapy drug candidates.

Multifunctional gold nanoparticle based selective detection of esophageal squamous cell carcinoma cells using resonance Rayleigh scattering assay

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China. Early and accurate diagnosis is the key to effective treatment of this disease. In this work, a resonance Rayleigh scattering (RRS) strategy was established to determine the concentration of epidermal growth factor receptor (EGFR) over-expressed ESCC cancer cells, which based on the selective binding of the anti-EGFR aptamer (Apt) and anti-EGFR antibody (Ab) multi-functionalized gold nanoparticles (AuNPs) probe (Apt-AuNPs-Ab) to the EGFR-positive cancer cell. When the probe was mixed with the Eca109 ESCC cancer cell, a distinct RRS intensity increase was observed. The probe possesses a dynamic range from 1.0 × 102-5.0 × 105 cell·mL−1 for Eca109 cells, and the detection limit is 20 cell·mL−1. Experimental results with the A2780 ovarian cancer cells line, as well as with the Eca109 ESCC cancer cell line, clearly demonstrated that the RRS assay was sensitive and selective to Eca109 than the other cancer cell lines that express a low level of EGFR. The proposed RRS assay provided a novel platform for detection of EGFR-positive cancer cells and shown the good potential for clinical diagnostics.

Multifunctional Gold Nanoparticles: A Novel Nanomaterial for Various Medical Applications and Biological Activities.

Nanotechnology has become a trending area in science and has made great advances with the development of functional, engineered nanoparticles. Various metal nanoparticles have been widely exploited for a wide range of medical applications. Among them, gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence and are highly remarkable. AuNPs, with their multiple, unique functional properties, and easy of synthesis, have attracted extensive attention. Their intrinsic features (optics, electronics, and physicochemical characteristics) can be altered by changing the characterization of the nanoparticles, such as shape, size and aspect ratio. They can be applied to a wide range of medical applications, including drug and gene delivery, photothermal therapy (PTT), photodynamic therapy (PDT) and radiation therapy (RT), diagnosis, X-ray imaging, computed tomography (CT) and other biological activities. However, to the best of our knowledge, there is no comprehensive review that summarized the applications of AuNPs in the medical field. Therefore, in this article we systematically review the methods of synthesis, the modification and characterization techniques of AuNPs, medical applications, and some biological activities of AuNPs, to provide a reference for future studies.

Biofabrication of gold nanoparticles with bone remodeling potential: an in vitro and in vivo assessment

Recent thrust in the biomaterials research has shifted towards developing bioactive and resorbable scaffolds with nanotechnological interventions. Next-generation bone scaffolds need to be multifunctional with desired osteo-integration ability, conformed resorption rate and in vivo imaging potential. In this study, we synthesized biogenic multifunctional gold nanoparticles (AuNPs) using immobilized crude enzyme (ImCE) of Bacillus licheniformis. The multifunctional characteristics of AuNPs and reusability of ImCE for AuNP synthesis can make the process and application cost-effective. ImCE catalyzed the bioreduction of gold ions to AuNPs of 18.4 ± 3.3 nm. AuNPs showed good hemocompatibility and antioxidant property without any toxic effects. Further, AuNPs demonstrated the increase in alkaline phosphatase activity and calcium deposition through MC3T3-E1 murine preosteoblast cell line and rat bone marrow stromal cells (BMSCs). The osteoinductive effect of AuNPs was also investigated in vivo wherein the composite cryogel scaffold functionalized with bone morphogenic protein-2 (rhBMP-2), zoledronic acid (ZA), and AuNPs was implanted in a muscle pouch of Wistar rats. AuNPs had synergistic effect on bone formation along with rhBMP-2 and ZA as seen from micro-computed tomography and histological analysis. The AuNPs were found to exhibit autofluorescence property and enhanced the degradation of scaffold at the implanted site in vivo. The developed process of using ImCE presents a novel approach for biogenic fabrication of AuNPs with the potential orthopedic application.

Recent advances in combinatorial cancer therapy via multifunctionalized gold nanoparticles.

The diverse behavior of nanogold in the therapeutic field is related to its unique size and shape. Nanogold offers improvements in modern diagnostic and therapeutic implications, increases disease specificity and targeted drug delivery, and is relatively economical compared with other chemotherapeutic protocols. The diagnosis of cancer and photothermal therapy improve drastically with the implementation of nanotechnology. Different types of nanoparticles, that is, gold silica nanoshells, nanorods and nanospheres of diverse shapes and geometries, are used widely in the photothermal therapy of cancerous cells and nodules. Numerous reviews have been published on the therapeutic applications of gold nanoparticles, but studies on combinatorial applications of nanogold in cancer therapy are limited. This review focuses on the combinatorial cancer therapy using optical properties of nanogold with different shapes and geometries, and their therapeutic applications in cancer diagnosis, photothermal therapy, cancer imaging and targeted drug delivery.

Multifuntional Gold Nanoparticles for the SERS Detection of Pathogens Combined with a LAMP-in-Microdroplets Approach.

We developed a droplet-based optofluidic system for the detection of foodborne pathogens. Specifically, the loop-mediated isothermal amplification (LAMP) technique was combined with surface-enhanced Raman scattering (SERS), which offers an excellent method for DNA ultradetection. However, the direct SERS detection of DNA compromises the simplicity of data interpretation due to the variability of its SERS fingerprints. Therefore, we designed an indirect SERS detection method using multifunctional gold nanoparticles (AuNPs) based on the formation of pyrophosphate generated during the DNA amplification by LAMP. Towards this goal, we prepared multifunctional AuNPs involving three components with key roles: (1) thiolated poly(ethylene glycol) as stabilizing agent, (2) 1-naphthalenethiol as Raman reporter, and (3) glutathione as a bioinspired chelating agent of magnesium (II) ions. Thus, the variation in the SERS signal of 1-naphthalenethiol was controlled by the aggregation of AuNPs triggered by the complexation of pyrophosphate and glutathione with free magnesium ions. Using this strategy, we detected Listeria monocytogenes, not only in buffer, but also in a food matrix (i.e., ultra-high temperaturemilk) enabled by the massive production of hotspots as a result of the self-assemblies that enhanced the SERS signal. This allowed the development of a microdroplet-LAMP-SERS platform with isothermal amplification and real-time identification capabilities.