pH-responsive Gold Nanoparticles Research Articles

Ultrasound imaging of renal fibrosis using gold nanoparticles

Abstract Introduction Microbubble ultrasound contrast agents have limitations due to their short circulation half-life and poor acoustic attenuation. In our previous study, pH-responsive gold nanoparticles (2∼3 nm) were optimized for ultrasound fluorescence molecular imaging of mouse kidneys. Renal fibrosis is associated with increased expression of the integrin αvβ3 receptor in neovascular endothelial cells. To address this, gold nanoparticles (cRGD-GSH-AuNPs) were synthesized by introducing RGD peptide, which specifically binds to integrin. Purpose The purpose of this study was to evaluate the potential of cRGD-GSH-AuNPs as a contrast agent for targeted ultrasound imaging of renal fibrosis. Methods Cyclic arginine-glycine-aspartic (cRGD) targeting integrin αvβ3 receptors was linked with glutathione (GSH)-modified gold nanoparticles (AuNPs) to create cRGD-GSH-AuNPs. After characterizing their physical properties and verifying their biocompatibility, GSH-AuNPs and cRGD-GSH-AuNPs were injected into mice with the renal fibrosis model. The renal imaging effect was evaluated by ultrasound and fluorescence imaging, and the targeting of the particles was confirmed by pathological tissue staining. Results The average size of cRGD-GSH-AuNPs determined by electron microscopy was 1.7 ± 0.2 nm, and the particles maintained biological stability after modification. The average ultrasound intensity of cRGD-GSH-AuNPs in the renal fibrosis group (22 ± 2 dB) was significantly higher than that of GSH-AuNPs in the fibrosis group (3.5 ± 3 dB), cRGD-GSH-AuNPs in the control group (1.5 ± 1 dB), and GSH-AuNPs in the control group (2 ± 1.5 dB) (all, P < 0.05). Intravenous injection of cRGD-GSH-AuNPs significantly enhanced the ultrasound signal intensity in fibrotic kidneys (see Figure 1). Conclusions Gold nanoparticles targeting integrin αVβ3 receptors achieve specific non-invasive imaging of renal fibrosis, and are a promising ultrasound contrast agent for the evaluation of renal fibrosis.Figure 1

131I labeled pH-responsive gold nanoparticles for bimodal tumor diagnosis

• Preparation of pH-responsive 131 I-labeled gold nano-particle molecular probe. • Aggregation of gold nanoparticles was explored based on the tumor microenvironment. • Dual-modality imaging further improves the diagnostic efficacy of tumors. Considering that each diagnostic method exhibits its disadvantages, such as the poor spatial resolution of SPECT and limited penetration depth of PA imaging, the development of a diagnosis integrated agent with dual-modality imaging performance is of great research interest. Herein, an interesting triggered mechanism, release, and aggregation of radiolabeled Au NPs were explored for tumor diagnosis based on the effect of H + in the tumor microenvironment. In vitro experiments reveal that the pH-responsive Au NPs exhibit an obvious accumulation effect and local surface plasmon resonance (LSPR) coupling effect and generate strong NIR absorption and can be used as the PA imaging agent. Importantly, Au aggregation only appears in the acid tumor microenvironment and displays excellent tumor SPECT diagnostic and photoacoustic imaging performance in vivo. This work provides a new synergistic strategy for SPECT and PA bimodal imaging to further improve the diagnostic efficacy of tumors.

Cancer Cell-Specific Enhanced Raman Imaging and Photothermal Therapeutic Effect Based on Reversibly pH-Responsive Gold Nanoparticles.

Stimuli-responsive nanoparticles are favorable for improving the selective delivery and rational vocation that easily avoids the undesirable barriers or side effects, leading to a further improved therapeutic efficiency. Furthermore, multifunctional nanomaterials have been extensively developed as attractive candidates for theranostic reagents for cancer treatment. In this article, we developed reversibly pH-responsive gold nanoparticles (AuNPs) with an enhanced Raman scattering signal as well as an efficient photothermal effect and demonstrated their applications as a theranostic reagent for cancer treatment. Surfaces of these AuNPs were modified with mixed layers of Cy3-modified single-stranded DNA (ssDNA-Cy3) for Raman probing and a negative charge supply and cytochrome C (Cyt C) for pH-responsive charge inversion. This combination of pH-responsive ligands and Raman probes played an important role in inducing the assembly or disassembly of AuNPs corresponding to the neighboring pH, accompanied by an additional highly distinguished Raman signal intensity. An operative reversible response of the AuNPs to pH is endowed with the characteristic behavior of AuNPs with the cancerous cell's acidic microenvironment of low pH. The responsive aggregation of AuNPs in a lower pH medium provides highly amplified signals attributed to well-formed hot spots between the particle surfaces that deliver better Raman scattering signals. The acidic pH-responsive aggregation of the particles also provided efficient photothermal treatments using a long-wavelength laser light with the benefit of deeper penetration for cancer cells. In vitro experiments employing cancer cells and control normal cells well-demonstrated the specificity of the particles to cancer cells in terms of highly enhanced Raman imaging and therapeutic efficiency.

Morphologically homogeneous, pH-responsive gold nanoparticles for non-invasive imaging of HeLa cancer

Gold nanoparticles (AuNPs) have been widely used as nanocarriers in drug delivery to improve the efficiency of chemotherapy treatment and enhance early disease detection. The advantages of AuNPs include their excellent biocompatibility, easy modification and functionalization, facile synthesis, low toxicity, and controllable particle size. This study aimed to synthesize a conjugated citraconic anhydride link between morphologically homogeneous AuNPs and doxorubicin (DOX) (DOX-AuNP). The carrier was radiolabeled for tumor diagnosis using positron emission tomography (PET). The systemically designed DOX-AuNP was cleaved at the citraconic anhydride linker site under the mild acidic conditions of a cancer cell, thereby releasing DOX. Subsequently, the AuNPs aggregated via electrostatic attraction. HeLa cancer cells exhibited a high uptake of the radiolabeled DOX-AuNP. Moreover, PET tumor images were obtained using radiolabeled DOX-AuNP in cancer xenograft mouse models. Therefore, DOX-AuNP is expected to provide a valuable insight into the use of radioligands to detect tumors using PET.

Hierarchical superstructures assembled from pH-responsive gold nanoparticles in deformable emulsion droplets.

Integrating stimuli-responsive nanoparticles (NPs) into shape-tunable hierarchical superstructures has emerged as a powerful way to fabricate smart materials. Here, we propose a robust strategy for the fabrication of sheet-like superlattices and hollow capsules by precisely tuning the interfacial tension of emulsion droplets containing pH-responsive gold nanoparticle building blocks, providing an efficient route to construct hierarchical superstructures with different applications.

Reversibly pH-responsive gold nanoparticles and their applications for photothermal cancer therapy

Microenvironment responsive nanomaterials are attractive for therapeutic applications with regional specificity. Here we report pH responsive gold nanoparticles which are designed to aggregate in acidic condition similar to cancer environment and returned to its original disassembled states in a physiological pH. The pH responsive behavior of the particles is derived by change of electrostatic interaction among the particles where attraction and repulsion play a major role in low and high pH of the environment, respectively. Since different electrostatic interaction behavior of the particles in varied pH is induced not by irreversible chemical change but by simple protonation differences, the pH responsive process of assembly and disassembly is totally reversible. The low pH specific aggregation of gold nanoparticles resulted in red shift of plasmonic absorption peak and showed higher photothermal efficacy in acidic pH than in normal physiological pH. The low pH specific photothermal effect with long wave laser irradiation was directly applied to cancer specific photothermal therapy and resulted higher therapeutic effect for melanoma cancer cells than non-pH responsive gold nanoparticles.

In Vitro Drug Release and Biocatalysis from pH-Responsive Gold Nanoparticles Synthesized Using Doxycycline.

pH-sensitive doxycycline gold nanoparticles (doxy-AuNPs) are reported here to act as effective drug nanocarriers and as biocatalysts. The AuNPs were synthesized with doxy as the reducing and capping agent. Various parameters were optimized to find the best conditions for the synthesis of doxy-AuNPs, and these were characterized with UV-vis, X-ray diffraction (XRD), FTIR, and transmission electron microscopy (TEM). Doxy-AuNPs were then loaded with the anticancer drug doxorubicin (DOX), where 70% of the initially available drug was loaded within 24 h. Furthermore, pH-dependent drug release was measured at 60% with in vitro measurements in phosphate-buffered saline (PBS). In addition, the doxy-AuNPs were applied as a biocatalyst. Oxidation of dopamine was taken as a model reaction to determine the catalytic activity of doxy-AuNPs. Almost complete oxidation of dopamine occurred in 5 min, which indicates the fast response of synthesized doxy-AuNPs as a biocatalyst. Hence, doxy-AuNPs are a versatile platform for drug loading and biocatalyst.

Redox and pH-responsive gold nanoparticles as a new platform for simultaneous triple anti-cancer drugs targeting

Cancer is considered to be one of the leading causes of morbidity and mortality worldwide and nanotechnology was shown to have a unique potential to enhance the therapeutic performance of anti-cancer agents. A novel dual stimuli-responsive polyethylene glycol (PEG) block copolymer was synthesized for the decoration and stabilization of gold nanoparticles (NPs) to carry multiple anti-cancer drugs, doxorubicin (DOX), methotrexate (MTX) and 6-mercaptopurine (MP). DOX, MTX and MP were successfully loaded (the loading capacity of 37%, 12%, and 49%, respectively) into the NPs by ionic interaction (DOX and MTX) and disulphide-covalent bond formation (MP) in the polymeric shell of NPs. Furthermore, the triggered drugs release ability of NPs was shown through the comparison of simulated physiological and tumor tissue environments. The enhanced efficiency of the developed NPs and their targeted performance via MTX (target ligand of folate receptors) decoration were illustrated through the various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry on various cancer cell lines with different levels of folate receptors. Our proposed idea in simultaneous delivery of three cytotoxic drugs with our newly designed PEGylated gold NPs may provide promising and novel prospect in cancer therapy.

Design of pH-responsive gold nanoparticles in oncology

Gold nanoparticles (AuNPs) hold promising applications in many fields such as electronics, optics and catalysis. In the past decades, there has been a growing interest for their application in medicine, in particular in nano-oncology as contrast agents, drug delivery vehicles or for diagnosis. Once injected intravenously and thanks to their small size, the AuNPs can circulate in the whole body via the blood stream and reach easily the tumour. However, what makes them very attractive for cancer treatment is their ability to distinguish healthy cells from cancer cells. While the current anticancer agents lack specific targeting, AuNPs, with their targeting efficiency, will enable the use of lower amount of drugs with all the positive aspects for the health of the patient. Additionally, their optical properties give them the ability to be used in imaging as an incredibly powerful contrast agent. For these reasons, they are believed to be one of the tools that, in the future, will enable to considerably increase the efficiency of cancer treatments by simultaneously imaging the tumour and treat it. They constitute an ideal theranostic drug delivery platform, in other words a unique combination of diagnostics and therapy. Many researches focus on the engineering of the nanoparticle surface in order to increase their biocompatibility and enable their further conjugation with bioactive ligands such as drugs, targeting or imaging agents for the design of multifunctional platforms. pH responsiveness, the ability to change properties with a change of proton concentration, is a remarkable asset for drug delivery carrier. Indeed, it has been demonstrated that cancer cells show very particular pHs in their environment: extracellular as well as intracellular. This characteristic has been exploited to create a more specific and efficient way to treat cancer. The present review focuses on the design of pH responsive AuNPs and particularly on the advantages and the potential applications of such hybrid nanomaterials in oncology.

Protein-coated pH-responsive gold nanoparticles: Microwave-assisted synthesis and surface charge-dependent anticancer activity.

The biocompatibility and ease of functionalization of gold nanoparticles underlie significant potential in biotechnology and biomedicine. Eight different proteins were examined in the preparation of gold nanoparticles (AuNPs) in aqueous medium under microwave irradiation. Six of the proteins resulted in the formation of AuNPs. The intrinsic pH of the proteins played an important role in AuNPs with strong surface plasmon bands. The hydrodynamic size of the nanoparticles was larger than the values observed by TEM and ImageJ. The formation of a protein layer on the AuNPs accounts for this difference. The AuNPs exhibited sensitivity towards varying pH conditions, which was confirmed by determining the difference in the isoelectric points studied by using pH-dependent zeta potential titration. Cytotoxicity studies revealed anticancerous effects of the AuNPs at a certain micromolar concentration by constraining the growth of cancer cells with different efficacies due to the use of different proteins as capping agents. The positively charged AuNPs are internalized by the cells to a greater level than the negatively charged AuNPs. These AuNPs synthesized with protein coating holds promise as anticancer agents and would help in providing a new paradigm in area of nanoparticles.

One-step method for preparation of pH-responsive gold nanoparticles with block copolymer shell structures by UV irradiation

Gold nanoparticles (AuNPs) are synthesized by UV irradiation of the solution of poly(2-vinyl pyridine)-block-poly(ethylene oxide)/HAuCl4 (PVP-b-PEO/HAuCl4) complexes. The AuNPs with cross-linked copolymer shells are stable in organic solvents and various biochemical buffers. It is found that AuNPs are pH sensitive. The average hydrodynamic diameter (Dh) of the AuNPs in water measured by dynamic light scattering (DLS) is affected by the pH value of buffers. The optical properties of the AuNPs are also sensitive to the solution pH due to structural changes of the copolymers. It is expected that AuNPs will be useful as plasmonic, light-scattering, and light-absorbing analogs.

Symmetric and asymmetric adsorption of pH-responsive gold nanoparticles onto microgel particles and dispersion characterisation

The interaction between carboxylic acid-stabilised gold nanoparticles (AuNP) and pH-responsive microgels is shown. The microgel particles are a copolymer of N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) and N-isopropylacrylamide (NIPAM). The microgel properties are presented by their hydrodynamic diameter and electrophoretic mobility in response to pH. These microgel particles are pH-responsive under neutral conditions decreasing in diameter beyond pH 7. The dispersion characteristics of AuNP adsorbed onto the microgel network are shown with respect to adsorbed amount and the pH-responsive properties of the AuNP. This data is presented between pH 3 and 6 where the microgel properties remain constant. Asymmetric adsorption of AuNP onto poly(DMAPMA-co-NIPAM) microgels is achieved by adsorption of nanoparticles, from the aqueous phase, onto microgel-stabilised oil-in-water emulsions. These asymmetrically modified microgels display very different dispersion behaviour, in response to pH, due to their dipolar nature.