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Death Pathways of Cancer Cells Modulated by Surface Molecule Density on Gold Nanorods.

ABSTRACT: Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρ_{surf. molecule} (N_{surf. molecules} /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρ_{surf. molecule} mainly induce apoptosis, while with large ρ_{surf. molecule} they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρ_{surf. molecule} due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρ_{surf. molecule} greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.

SUBMITTER: Zhang F

PROVIDER: S-EPMC8596106 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The immune system may respond to engineered nanomaterials (ENM) through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres. Exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation.

2023-05-29 | GSE233641 | GEO

Impact of Surface Charge-Tailored Gold Nanorods for Selective Targeting of Mitochondria in Breast Cancer Cells Using Photodynamic Therapy.

Project description:Herein, the impact of surface charge tailored of gold nanorods (GNRs) on breast cancer cells (MCF-7 and MDA-MB-231) upon conjugation with triphenylphosphonium (TPP) for improved photodynamic therapy (PDT) targeting mitochondria was studied. The salient features of the study are as follows: (i) positive (CTAB@GNRs) and negative (PSS-CTAB@GNRs) surface-charged gold nanorods were developed and characterized; (ii) the mitochondrial targeting efficiency of gold nanorods was improved by conjugating TPP molecules; (iii) the conjugated nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) were evaluated for PDT in the presence of photosensitizer (PS), 5-aminolevulinic acid (5-ALA) in breast cancer cells; (iv) both nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) induce apoptosis, damage DNA, generate reactive oxygen species, and decrease mitochondrial membrane potential upon 5-ALA-based PDT; and (v) 5-ALA-PDT of two nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) impact cell signaling (PI3K/AKT) pathway by upregulating proapoptotic genes and proteins. Based on the results, we confirm that the positively charged (rapid) nanoprobes are more advantageous than their negatively (slow) charged nanoprobes. However, depending on the kind and degree of cancer, both nanoprobes can serve as efficient agents for delivering anticancer therapy.

| S-EPMC10515365 | biostudies-literature

Anchoring Effects of Surface Chemistry on Gold Nanorods: Modulates Autophagy.

Project description:Gold nanorods (Au NRs) have been receiving extensive attention owing to their extremely attractive properties which make them suitable for various biomedical applications. Au NRs could induce nano-toxicity, but this trouble could turn into therapeutic potential through tuning the autophagy. However, the autophagy-inducing activity and mechanism of Au NRs is still unclear. Here we showed that surface chemical modification can tune the autophagy-inducing activity of Au NRs in human lung adenocarcinoma A549 cells. CTAB-coated Au NRs induce remarkable levels of autophagy activity as evidenced by LC3-II conversion and p62 degradation, while PSS- and PDDAC-coated Au NRs barely induce autophagy. More importantly, we also demonstrated that the AKT-mTOR signaling pathway was responsible for CTAB-coated Au NRs-induced autophagy. We furthermore showed that CTAB-coated Au NRs also induces autophagy in human fetal lung fibroblast MRC-5 cells in a time-dependent manner. This study unveils a previously unknown function for Au NRs in autophagy induction, and provides a new insight for designing surface modifications of Au NRs for biomedical applications.

| S-EPMC4539969 | biostudies-literature

Project description:The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization.

| S-EPMC9145314 | biostudies-literature

Polydopamine-enabled surface functionalization of gold nanorods for cancer cell-targeted imaging and photothermal therapy.

Project description:AimA novel biomimetic strategy was employed for presenting antibodies on gold nanorods (NRs) to target growth factor receptors on cancer cells for use in photothermal therapy.Materials & methodsPolydopamine (PD) was polymerized onto gold NRs, and EGF receptor antibodies (anti-EGFR) were immobilized onto the layer. Cell-binding affinity and light-activated cell death of cancer cells incubated with anti-EGFR-PD-NRs were quantified by optical imaging.ResultsPD was deposited onto gold NRs, and antibodies were bound to PD-coated NRs. Anti-EGFR-PD-NRs were stable in media, and were specifically bound to EGFR-overexpressing cells. Illumination of cells targeted with anti-EGFR-PD-NRs enhanced cell death compared with nonirradiated controls and cells treated with antibody-free NRs.ConclusionPD facilitates the surface functionalization of gold NRs with biomolecules, allowing cell targeting and photothermal killing of cancer cells. PD can potentially coat a large variety of nanoparticles with targeting ligands as a strategy for biofunctionalization of diagnostic and therapeutic nanoparticles.

| S-EPMC3530415 | biostudies-literature

Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods.

Project description:We demonstrate the use of gold nanorods as bright contrast agents for two-photon luminescence (TPL) imaging of cancer cells in a three-dimensional tissue phantom down to 75 mum deep. The TPL intensity from gold-nanorod-labeled cancer cells is 3 orders of magnitude brighter than the two-photon autofluorescence (TPAF) emission intensity from unlabeled cancer cells at 760 nm excitation light. Their strong signal, resistance to photobleaching, chemical stability, ease of synthesis, simplicity of conjugation chemistry, and biocompatibility make gold nanorods an attractive contrast agent for two-photon imaging of epithelial cancer.

| S-EPMC2743599 | biostudies-literature

SPR signals enhancement by gold nanorods for cell surface marker detection.

Project description:Introduction: The detection of micrometer-sized particles like cells is limited by surface plasmon resonance (SPR) biosensors because of having a depth of evanescent wave <500 nm. In this study, for the first time, we exhibited the use of streptavidin-functionalized gold nanorods (GNRs) as intensification labels for detection of cell surface markers in SPR-based biosensors. Methods: The GNRs (ʎ max: 735 nm) were modified with streptavidin using EDC/NHS coupling method and human umbilical vein endothelial cells (HUVECs) were selected as the cell model for detecting VE-cadherin on cell surface using real-time SPR device in the 785 nm wavelength of the laser source. Results: The investigations revealed that the plasmonic field extension produced from the gold layer and GNRs resulted in multiple enhancement of SPR signals when the wavelength of laser source in SPR instrument was matched with the wavelength of maximum absorbance in GNRs. Moreover, the results showed that the growth of ∆RU value in specific and non-specific bindings for various cell number injections were produced with increasing the cell number. Conclusion: The results displayed that cell detection can be performed in real- time form without any need to a time-consuming process used in conventional methods like immunocytochemistry, flow cytometry, and western blotting.

| S-EPMC6637213 | biostudies-literature

Project description:Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods

| PRJNA977066 | ENA

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Project description:Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

| S-EPMC10283337 | biostudies-literature

Photothermal Ablation of Cancer Cells by Albumin-Modified Gold Nanorods and Activation of Dendritic Cells.

Project description:Nanoparticle-mediated photothermal therapy has been widely studied for cancer treatment. It is important to disclose how photothermally ablated tumor cells trigger immune responses. In this study, bovine serum albumin (BSA)-coated gold nanorods (BSA-coated AuNRs) were prepared and used for photothermal ablation of breast tumor cells. The BSA-coated AuNRs showed high photothermal conversion efficiency and good photothermal ablation effect towards tumor cells. The ablated tumor cells were co-cultured with immature dendritic cells (DCs) through a direct cell contacting model and diffusion model to confirm the stimulatory effects of cell⁻cell interaction and soluble factors released from ablated tumor cells. The results indicated that photothermally ablated tumor cells induced immune-stimulatory responses of DCs through both cell⁻cell interaction and soluble factors. The results should be useful for synergistic photothermal-immunotherapy of primary and metastatic cancer.

| S-EPMC6337519 | biostudies-literature

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