Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang J
PROVIDER: S-EPMC8255032 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca2+-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the lactating mammary gland. The protein possesses a single strong Ca2+-binding site, which can also bind Mg2+, Mn2+, Na+, K+, and some other metal cations. It contains several distinct Zn2+-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions, α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca2+, increases stability of α-LA against the action of heat, various denaturing agents and proteases, while the binding of Zn2+ to the Ca2+-loaded protein decreases its stability and causes its aggregation. At pH 2, the protein is in the classical molten globule state. α-LA can associate with membranes at neutral or slightly acidic pH at physiological temperatures. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. Some of these aggregated states of α-LA can be used in practical applications such as drug delivery to tissues and organs. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid are cytotoxic to various tumor and bacterial cells. α-LA in the cytotoxic complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor and bacterial cells across the cell membrane. Perhaps in the future the complexes of α-LA with oleic acid will be used for development of new anti-cancer drugs.
| S-EPMC7565966 | biostudies-literature
Project description:Rationale: Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment. Methods: In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the OMCAPs@ rBSA-FA@IR780 nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Results: Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze H2O2 located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study in vitro and in vivo, our fabricated nanoprobes based on carbon-gold hybrid (OMCAPs@ rBSA-FA@IR780) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor. Conclusion: All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics.
| S-EPMC6587161 | biostudies-other
Project description:BackgroundMost colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context.ObjectiveTo investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease.MethodHAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells.ResultsPeroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development.ConclusionsThese data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.
| S-EPMC3888589 | biostudies-literature
Project description:Alpha-lactalbumin (α-LA) and binding of zinc cations to protein were studied. Molecular characteristics of protein was determined by MALDI-TOF/MS and electrophoresis SDS-PAGE, and also, for complexes, it was determined by spectroscopic techniques (ATR-FT-IR and Raman) and microscopic techniques (SEM along with an EDX detector and also TEM). The pH dependence of zeta potential of α-LA was determined in saline solution. The zinc binding to the protein mechanism was investigated; zinc binding to protein kinetics, the molecular modeling by the DFT method, and electron microscopy (SEM and TEM) for microstructure observation were performed. The experiments performed indicate a quick binding process (equilibrium takes place after 2 min of incubation) which occurs onto the surface of α-LA. Zinc cations change the conformation of the protein and create spherical particles from the morphological point of view. DFT studies indicate the participation of acidic functional groups of the protein (aspartic acid and glutamic acid residues), and these have a decisive influence on the interaction with zinc cations. Application studies of general toxicity and cytotoxicity and bioavailability were conducted.
| S-EPMC9631873 | biostudies-literature
Project description:Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles' potential clinical applications.
| S-EPMC4142062 | biostudies-literature
Project description:Gold nanoparticles-enabled intracellular surface-enhanced Raman spectroscopy (SERS) provides a sensitive and promising technique for single cell analysis. Compared with spherical gold nanoparticles, gold nanoflowers, i.e., flower-shaped gold nanostructures, can produce a stronger SERS signal. Current exploration of gold nanoflowers for intracellular SERS has been considerably limited by the difficulties in preparation, as well as background signal and cytotoxicity arising from the surfactant capping layer. Recently, we have developed a facile and surfactant-free method for fabricating hollow-channel gold nanoflowers (HAuNFs) with great single-particle SERS activity. In this paper, we investigate the cellular uptake and cytotoxicity of our HAuNFs using a RAW 264.7 macrophage cell line, and have observed effective cellular internalization and low cytotoxicity. We have further engineered our HAuNFs into SERS-active tags, and demonstrated the functionality of the obtained tags as trimodal nanoprobes for dark-field and fluorescence microscopy imaging, together with intracellular SERS.
| S-EPMC6121537 | biostudies-literature
Project description:Nanoprobes have been increasingly applied in the biomedical field due to their superior optical, electronic, or magnetic properties. Among the many aspects involved in the interaction between nanoprobes and biospecimens, size plays an essential role. Although the influence of size on their internalization behavior and distribution in live cells has been extensively studied, how does the size affect penetration of nanoprobes into fixed cells remains unknown. We investigate here the influence of size on the penetration behavior of gold nanoprobes into fixed mammalian cells by dark-field microscopy and surface-enhanced Raman scattering (SERS) microspectroscopy. We show that 14, 20, and 29 nm nanoprobes can readily enter into methanol-fixed MCF-7 cells, while 42 and 55 nm nanoprobes cannot cross the cell membrane. For 4% paraformaldehyde-fixed cells, even 14 nm nanoprobes can hardly get into the cells, but after treatment with permeabilization reagents, 14 and 20 nm nanoprobes are permitted to enter the cells. These findings provide important implications in future design of nanoprobes for cellular immunostaining.
| S-EPMC7876832 | biostudies-literature
Project description:BACKGROUND:The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900-1700?nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. METHODS:SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. RESULTS:Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. CONCLUSIONS:The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.
| S-EPMC7654009 | biostudies-literature
Project description:Selective thermal precipitation followed by a mechanical separation step is a well described method for fractionation of the main whey proteins, α-lactalbumin (α-la) and β-lactoglobulin (β-lg). By choosing appropriate environmental conditions the thermal precipitation of either α-la or β-lg can be induced. Whereas β-lg irreversibly aggregates, the precipitated α-la can be resolubilized by a subsequent adjustment of the solution's pH and the ionic composition. This study reports on the analytical characterization of resolubilized α-la compared to its native counterpart as a reference in order to assess whether the resolubilized α-la can be considered close to 'native'. Turbidity and quantification by RP-HPLC of the resolubilized α-la solutions were used as a measure of solubility in aqueous environment. RP-HPLC was also applied to determine the elution time as a measure for protein's hydrophobicity. DSC measurement was performed to determine the denaturation peak temperature of resolubilized α-la. FTIR spectroscopy provided insights in the secondary structure. The refolding of α-la achieved best results using pH 8.0 and a 3-fold stoichiometric amount of Ca2+ per α-la molecule. The results showed that the mechanism of aggregation induced by gentle thermal treatment under acidic conditions with subsequent mechanical separation is reversible to a certain extent, however, the exact native conformation was not restored.
| S-EPMC8465387 | biostudies-literature
Project description:A simple, cost-effective yet rapid and sensitive sensor for on-site and real-time Hg(2+) detection based on bovine serum albumin functionalized fluorescent gold nanoparticles as novel and environmentally friendly fluorescent probes was developed. Using this probe, aqueous Hg(2+) can be detected at 0.1 nM in a facile way based on fluorescence quenching. This probe was also applied to determine the Hg(2+) in the lake samples, and the results demonstrate low interference and high sensitivity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11671-010-9730-y) contains supplementary material, which is available to authorized users.
| S-EPMC2964487 | biostudies-literature