Destruction Of Breast Cancer Cells Research Articles

Study of optical properties of gold nanoparticles embedded in normal, benign, and malignant breast tissues

In this work, the complex dielectric permittivity of breast tissue is calculated for different growth rates of benign and malignant tumors using the Maxwell Garnett (MG) effective medium theory. The results show a wide variability of the dielectric properties depending on the nature and the volume fraction of the cancer cells. The benign-normal and malignant-normal heterostructures are denoted respectively x-B/N and x-M/N where x is the volume fraction of cancer cells in the breast tissue. The real and imaginary parts of dielectric permittivity increases when the growth rates of benign and malignant tumors increase and decrease when the microwave frequency increases from 0.5 to 8 GHz. In the aim to use the gold nanoparticles (GNPs) in breast cancer therapy, both for a better image diagnostic and photothermal therapy (PTT), we present here a study on the optical properties of GNPs embedded in normal, benign and malignant breast tissue in the frequency range from 0.5 GHz to 8 GHz. optical band gap energy for GNP is located in [0.5eV−1.46eV](±0.06eV), [0.72eV−1.20eV](±0.04eV) and [0.11eV−0.74eV](±0.02eV) ranges for Normal, Benign and Malignant breast tissues, respectively. We use the Finite Element Method (FEM) to evaluate the spectra of the dielectric and optical parameters of GNPs namely: complex dielectric permittivity, absorption cross section, reflectivity, dielectric loss function and conductivity, the surface plasmons resonance (SPR) properties are deduced from these spectra. The obtained results show that the SPR-peak of the GNPs is located in the Visible (Vis), near infrared (NIR) and short wavelength infrared (SWIR) bands when they are embedded respectively in the normal, benign and malignant breast tissue. For these three tissues when the microwave frequency increases from 0.5 to 8 GHz, the SPR-peak position λmax shifts towards the short wavelengths. The calculations show that in the vicinity of λmax the dielectric loss function take a maximum value and the reflectivity change strongly. These results show that the absorption and dielectric loss peaks are less wide for the high microwave frequencies and very wide for the low frequencies, which also influences the difference between the asymptotic values of the real part of permittivity and of the reflectivity. These results make it possible to identify the nature of the breast tumor using the GNPs in the sensors based on the of SPR phenomenon. The optical properties of GNPs depending on their size and on the tumor growth rate in the breast tissue are also studied and discussed. The study carried out represents a feasibility proposal for the use of GNPs for determining the degree of breast tumor progression and estimate the good performance of using the GNPs for the selective destruction of breast cancer cells.

Oleandrin, a cardiac glycoside, induces immunogenic cell death via the PERK/elF2\u03b1/ATF4/CHOP pathway in breast cancer

Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting anti-tumor immune surveillance. The cardiac glycoside oleandrin, which inhibits Na+/K+-ATPase pump (NKP), has been shown to suppress breast cancer growth via inducing apoptosis. In the present study, we showed that oleandrin treatment triggered breast cancer cell ICD by inducing calreticulin (CRT) exposure on cell surface and the release of high-mobility group protein B1 (HMGB1), heat shock protein 70/90 (HSP70/90), and adenosine triphosphate (ATP). The maturation and activation of dendritic cells (DCs) were increased by co-culturing with the oleandrin-treated cancer cells, which subsequently enhanced CD8+ T cell cytotoxicity. Murine breast cancer cell line EMT6 was engrafted into BALB/c mice, and tumor-bearing mice were administered with oleandrin intraperitoneally every day. Oleandrin inhibited tumor growth and increased tumor infiltrating lymphocytes including DCs and T cells. Furthermore, the differential mRNA expression incurred by oleandrin was investigated by mRNA sequencing and subsequently confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Mechanistically, oleandrin induced endoplasmic reticulum (ER) stress-associated, caspase-independent ICD mainly through PERK/elF2α/ATF4/CHOP pathway. Pharmacological and genetic inhibition of protein kinase R-like ER kinase (PERK) suppressed oleandrin-triggered ICD. Taken together, our findings showed that oleandrin triggered ER stress and induced ICD-mediated immune destruction of breast cancer cells. Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.

Layer-by-layer assembly of graphene oxide on thermosensitive liposomes for photo-chemotherapy.

Stimuli sensitive hybrid nanoparticles have been synthesized using a layer-by-layer technique and demonstrated for dual chemo-photothermal destruction of breast cancer cells. The hybrid nanoparticles are composed of alternating layers of graphene oxide and graphene oxide conjugated poly-l-lysine coating the surface of a thermosensitive cationic liposome containing doxorubicin as a core. Data suggests that the hybrid nanoparticles may offer many advantages for chemo-photothermal therapy. Advantages include a decrease of the initial burst release which may result in the reduction in systemic toxicity, increase in pH responsivity around the tumor environment and improved NIR light absorption.

Gold nanoparticle-enhanced Photodynamic therapy: Effects of Surface Charge and Mitochondrial Targeting

The authors aimed to further improve the efficiency and selectivity of gold nanoparticle (Au NP)-assisted photodynamic therapy by modulating the surface charge of Au NPs and delivering Au NPs particularly to mitochondria of breast cancer cells. Solid gold nanospheres (˜50 nm) with negative and positive surface charge were synthesized respectively, and mitochondria-targeting Au NPs were prepared by conjugating with triphenylphosphonium molecules. Positively charged Au NPs were preferably taken up by breast cancer cells. Combination of positive surface charge with mitochondria-targeting domain onto Au NPs allowed their accumulation in the mitochondria of breast cancer cells to significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid-enabled photodynamic therapy and improve selective destruction of breast cancer cells.

Detection of human leukocyte antigen biomarkers in breast cancer utilizing label-free biosensor technology.

According to the American Cancer Society, more than 200,000 women will be diagnosed with invasive breast cancer each year and approximately 40,000 will die from the disease. The human leukocyte antigen (HLA) class I samples peptides derived from proteasomal degradation of cellular proteins and presents these fragments on the cell surface for interrogation by circulating cytotoxic T lymphocytes (CTL). Generation of T-cell receptor mimic (TCRm) monoclonal antibodies (mAbs) which recognize breast cancer specific peptide/HLA-A*02:01 complexes such as those derived from macrophage migration inhibitory factor (MIF19-27) and NY-ESO-1157-165 enable detection and destruction of breast cancer cells in the absence of an effective anti-tumor CTL response. Intact class I HLA/peptide complexes are shed by breast cancer cells and represent potentially relevant cancer biomarkers. In this work, a breakthrough biomarker screening system for cancer diagnostics incorporating T-cell receptor mimic monoclonal antibodies combined with a novel, label-free biosensor utilizing guided-mode resonance (GMR) sensor technology is presented. Detection of shed MIF/HLA-A*02:01 complexes in MDA-MB-231 cell supernatants, spiked human serum, and patient plasma is demonstrated. The impact of this work could revolutionize personalized medicine through development of companion disease diagnostics for targeted immunotherapies.

Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology

According to the American Cancer Society, more than 200,000 women will be diagnosed with invasive breast cancer each year and approximately 40,000 will die from the disease. The human leukocyte antigen (HLA) class I samples peptides derived from proteasomal degradation of cellular proteins and presents these fragments on the cell surface for interrogation by circulating cytotoxic T lymphocytes (CTL). Generation of T-cell receptor mimic (TCRm) monoclonal antibodies (mAbs) which recognize breast cancer specific peptide/HLA-A*02:01 complexes such as those derived from macrophage migration inhibitory factor (MIF19-27) and NY-ESO-1157-165 enable detection and destruction of breast cancer cells in the absence of an effective anti-tumor CTL response. Intact class I HLA/peptide complexes are shed by breast cancer cells and represent potentially relevant cancer biomarkers. In this work, a breakthrough biomarker screening system for cancer diagnostics incorporating T-cell receptor mimic monoclonal antibodies combined with a novel, label-free biosensor utilizing guided-mode resonance (GMR) sensor technology is presented. Detection of shed MIF/HLA-A*02:01 complexes in MDA-MB-231 cell supernatants, spiked human serum, and patient plasma is demonstrated. The impact of this work could revolutionize personalized medicine through development of companion disease diagnostics for targeted immunotherapies.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy.

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

BackgroundNanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells.MethodsThe complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining.ResultsUsing a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously.ConclusionWe have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy.

Gold Nanocages for Biomedical Applications.

Nanostructured materials provide a promising platform for early cancer detection and treatment. Here we highlight recent advances in the synthesis and use of Au nanocages for such biomedical applications. Gold nanocages represent a novel class of nanostructures, which can be prepared via a remarkably simple route based on the galvanic replacement reaction between Ag nanocubes and HAuCl(4). The Au nanocages have a tunable surface plasmon resonance peak that extends into the near-infrared, where the optical attenuation caused by blood and soft tissue is essentially negligible. They are also biocompatible and present a well-established surface for easy functionalization. We have tailored the scattering and absorption cross-sections of Au nanocages for use in optical coherence tomography and photothermal treatment, respectively. Our preliminary studies show greatly improved spectroscopic image contrast for tissue phantoms containing Au nanocages. Our most recent results also demonstrate the photothermal destruction of breast cancer cells in vitro by using immuno-targeted Au nanocages as an effective photo-thermal transducer. These experiments suggest that Au nanocages may be a new class of nanometer-sized agents for cancer diagnosis and therapy.

Gold Nanocages for Cancer Detection and Treatment

Gold nanocages represent a novel class of biocompatible vectors with potential applications in drug delivery, tumor/tissue imaging and photothermal therapy. They are prepared through the galvanic-replacement reaction between Ag nanostructures and HAuCl(4). By controlling the amount of HAuCl(4) added, we can tune the surface-plasmon resonance peaks of the Au nanocages into the near-infrared, where the attenuation of light by blood and soft tissue is relatively low. Here, we highlight recent advances in the synthesis and utilization of Au nanocages for cancer detection and treatment. We have tailored the optical properties of Au nanocages for use as contrast agents in optical coherence tomography and as transducers for the selective photothermal ablation of cancer cells. Our results show improved optical coherence tomography image contrast when Au nanocages are added to tissue phantoms as well as the selective photothermal destruction of breast cancer cells in vitro when immunotargeted Au nanocages are used.

Integrated molecular targeting of IGF1R and HER2 surface receptors and destruction ofbreast cancer cells using single wall carbon nanotubes

Molecular targeting and photodynamic therapy have shown great potential for selectivecancer therapy. We hypothesized that monoclonal antibodies that are specificto the IGF1 receptor and HER2 cell surface antigens could be bound to singlewall carbon nanotubes (SWCNT) in order to concentrate SWCNT on breastcancer cells for specific near-infrared phototherapy. SWCNT functionalized withHER2 and IGF1R specific antibodies showed selective attachment to breast cancercells compared to SWCNT functionalized with non-specific antibodies. Afterthe complexes were attached to specific cancer cells, SWCNT were excited by∼808 nm infraredphotons at ∼800 mW cm−2 for 3 min. Viability after phototherapy was determined by Trypan blue exclusion. Cellsincubated with SWCNT/non-specific antibody hybrids were still alive after photo-thermaltreatment due to the lack of SWNT binding to the cell membrane. All cancerous cellstreated with IGF1R and HER2 specific antibody/SWCNT hybrids and receivinginfrared photons showed cell death after the laser excitation. Quantitative analysisdemonstrated that all the cells treated with SWCNT/IGF1R and HER2 specificantibody complex were completely destroyed, while more than 80% of the cells withSWCNT/non-specific antibody hybrids remained alive. Following multi-componenttargeting of IGF1R and HER2 surface receptors, integrated photo-thermal therapy inbreast cancer cells led to the complete destruction of cancer cells. FunctionalizingSWCNT with antibodies in combination with their intrinsic optical properties cantherefore lead to a new class of molecular delivery and cancer therapeutic systems.

Pregnancy‐associated alpha2 glycoprotein (α2PAG) synthesis by human breast cancer tissue and cultured cell lines

AbstractElevated α2PAG serum levels are found in pregnant women and patients with diverse types of neoplasms including breast cancer. Primary human breast cancer tissue, MCF‐7 and BT‐20 human breast cancer cultured cell lines were shown to synthesize α2PAG in vitro. BT‐20 breast cancer cells also released this pregnancy‐associated protein. Synthesis was demonstrated by l‐[14C]‐leucine incorporation into immunochemically isolated protein and confirmed by radioimmunodiffusion and radioimmuno‐electrophoresis. These data (1) provide direct evidence for α2PAG synthesis by well‐characterized human breast cancer cells per se;(2) strongly suggest that at least part of the α22PAG synthesis observed in primary human breast cancer tissue in vitro was due specifically to breast cancer cells rather than exclusively to monocytes/mac‐rophages known to infiltrate neoplastic tissues and to produce this protein during pregnancy; and (3) are consistent with the conclusion that serum α2PAG is a definite breast cancer “marker protein” which originates from and reflects breast cancer status. On the basis of the association of elevated serum α2PAG levels in breast cancer patients, its known immunosuppressive activity in vitro, and the direct evidence for α2PAG synthesis by human breast cancer cells perse, we postulate that this protein plays an important immunoregulatory role in vivo to prevent immune rejection and/or destruction of breast cancer cells.