26 research outputs found

    Efficacy versus Toxicity - The Ying and Yang in Translating Nanomedicines

    Get PDF
    Nanomedicine, as a relatively new offshoot of nanotechnology, has presented vast opportunities in biomedical research for developing novel strategies to treat diseases. In the past decade, there has been a significant increase in in vitro and preclinical studies addressing the benefits of nanomedicines. In this commentary, we focus specifically on the efficacy- and toxicity-related translational challenges of nanocarrier-mediated systems, and briefly discuss possible strategies for addressing such issues at in vitro and preclinical stages. We address questions related specifically to the balance between toxicity and efficacy, a balance that is expected to be substantially different for nanomedicines compared to that for a free drug. Using case studies, we propose a ratiometric assessment tool to quantify the overall benefit of nanomedicine as compared to free drugs in terms of efficacy and toxicity. The overall goal of this commentary is to emphasize the strategies that promote the translation of nanomedicines, especially by learning lessons from previous translational failures of other drugs and devices, and to apply these lessons to critically assess data at the basic stages of nanomedicinal research

    Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

    Get PDF
    Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ~5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2˜83.97 eV and Au 4f5/2~87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ~1 nm and protein cluster aggregates of size ~8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ~674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 µg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer

    Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene

    No full text
    We report the effect of carboxyl functionalization of graphene in pacifying its strong hydrophobic interaction with cells and associated toxic effects. Pristine graphene was found to accumulate on the cell membrane causing high oxidative stress leading to apoptosis, whereas carboxyl functionalized hydrophilic graphene was internalized by the cells without causing any toxicity

    Luminescent quantum clusters of gold in bulk by albumin-induced core etching of nanoparticles: metal ion sensing, metal-enhanced luminescence, and biolabeling

    No full text
    The synthesis of a luminescent quantum cluster (QC) of gold with a quantum yield of ~4 % is reported. It was synthesized in gram quantities by the core etching of mercaptosuccinic acid protected gold nanoparticles by bovine serum albumin (BSA), abbreviated as AuQC@BSA. The cluster was characterized and a core of Au38 was assigned tentatively from mass spectrometric analysis. Luminescence of the QC is exploited as a "turn-off" sensor for Cu2+ ions and a "turn-on" sensor for glutathione detection. Metal-enhanced luminescence (MEL) of this QC in the presence of silver nanoparticles is demonstrated and a ninefold maximum enhancement is seen. This is the first report of the observation of MEL from QCs. Folic acid conjugated AuQC@BSA was found to be internalized to a significant extent by oral carcinoma KB cells through folic acid mediated endocytosis. The inherent luminescence of the internalized AuQC@BSA was used in cell imaging

    Protein Nanomedicine Exerts Cytotoxicity toward CD34<sup>+</sup> CD38<sup>–</sup> CD123<sup>+</sup> Leukemic Stem Cells

    No full text
    The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34<sup>+</sup> CD38<sup>–</sup> CD123<sup>+</sup> LSC and non-LSC “leukemic blast” compartments, without inducing myelosuppression or hemotoxicity. Besides, NV also exerted excellent synergistic lethality against leukemic bone marrow cells (BMC) at lower concentrations (0.1 μM) in combination with DNA methyltransferase (DNMT) inhibitor, decitabine. Considering the extermination of resilient LSC and synergism with decitabine, NV shows promise for clinical translation in the setting of a more tolerable and effective epigenetic targeted therapy for leukemia

    Green Synthesis of Anisotropic Gold Nanoparticles for Photothermal Therapy of Cancer

    No full text
    Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800–1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm<sup>2</sup> proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy

    Biocompatible Magnetite/Gold Nanohybrid Contrast Agents via Green Chemistry for MRI and CT Bioimaging

    No full text
    Magnetite/gold (Fe<sub>3</sub>O<sub>4</sub>/Au) hybrid nanoparticles were synthesized from a single iron precursor (ferric chloride) through a green chemistry route using grape seed proanthocyanidin as the reducing agent. Structural and physicochemical characterization proved the nanohybrid to be crystalline, with spherical morphology and size ∼35 nm. Magnetic resonance imaging and magnetization studies revealed that the Fe<sub>3</sub>O<sub>4</sub> component of the hybrid provided superparamagnetism, with dark T<sub>2</sub> contrast and high relaxivity (124.2 ± 3.02 mM<sup>–1</sup> s<sup>–1</sup>). Phantom computed tomographic imaging demonstrated good X-ray contrast, which can be attributed to the presence of the nanogold component in the hybrid. Considering the potential application of this bimodal nanoconstruct for stem cell tracking and imaging, we have conducted compatibility studies on human Mesenchymal Stem Cells (hMSCs), wherein cell viability, apoptosis, and intracellular reactive oxygen species (ROS) generation due to the particle–cell interaction were asessed. It was noted that the material showed good biocompatibility even for high concentrations of 500 μg/mL and up to 48 h incubation, with no apoptotic signals or ROS generation. Cellular uptake of the nanomaterial was visualized using confocal microscopy and prussian blue staining. The presence of the nanohybrids were clearly visualized in the intracytoplasmic region of the cell, which is desirable for efficient imaging of stem cells in addition to the cytocompatible nature of the hybrids. Our work is a good demonstrative example of the use of green aqueous chemistry through the employment of phytochemicals for the room temperature synthesis of complex hybrid nanomaterials with multimodal functionalities
    corecore