scholarly journals A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach

2020 ◽  
Vol 21 (24) ◽  
pp. 9681
Author(s):  
Eduardo Costa ◽  
Tânia Ferreira-Gonçalves ◽  
Miguel Cardoso ◽  
João M. P. Coelho ◽  
Maria Manuela Gaspar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Experimental Model ◽  
Near Infrared ◽  
Experimental Models ◽  
Female Rats ◽  
Breast Cancer Surgery ◽  
Preliminary Treatment ◽  
Sprague Dawley

Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors’ etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650–900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.

scholarly journals The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 71
Author(s):  
Tânia Ferreira-Gonçalves ◽  
Maria Manuela Gaspar ◽  
João M. P. Coelho ◽  
Vanda Marques ◽  
Ana S. Viana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Rosmarinic Acid ◽  
Near Infrared ◽  
Active Role ◽  
Synthetic Method ◽  
Tumor Cell Death ◽  
Maximum Absorbance

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer.

scholarly journals Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1094
Author(s):  
Allan Radaic ◽  
Nam E. Joo ◽  
Soo-Hwan Jeong ◽  
Seong-II Yoo ◽  
Nicholas Kotov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Biomedical Applications ◽  
Therapeutic Potential ◽  
Control Treatment ◽  
Track Record ◽  
Males And Females ◽  
Breast And Prostate Cancer ◽  
First Time

Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy.

Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model

Lab on a Chip ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. 735-744 ◽  
Author(s):  
Yamin Yang ◽  
Xiaochuan Yang ◽  
Jin Zou ◽  
Chao Jia ◽  
Yue Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Photodynamic Therapy ◽  
Three Dimensional ◽  
Therapeutic Agents ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Tissue Model

A microfluidic-based in vitro three-dimensional (3D) breast cancer tissue model was established for determining the efficiency of photodynamic therapy (PDT) with therapeutic agents (photosensitizer and gold nanoparticles) under various irradiation conditions.

scholarly journals An Experimental Model of Breast Cancer Cells: Informative Protocol for In Vitro Culture

2018 ◽  
Vol 38 (11) ◽  
pp. 6237-6245 ◽  
Author(s):  
XINXIN DU ◽  
KRISTINA KLASCHIK ◽  
PETER MALLMANN ◽  
EVGENIA ISACHENKO ◽  
GOHAR RAHIMI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Vitro Culture ◽  
Cancer Cells ◽  
Experimental Model ◽  
Breast Cancer Cells

scholarly journals Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation

2022 ◽  
Vol 23 (1) ◽  
pp. 547
Author(s):  
Jun H. Heo ◽  
Sang R. Lee ◽  
Seong Lae Jo ◽  
Hyun Yang ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Patients ◽  
Cardiovascular Effects ◽  
Female Rats ◽  
Acid Oxidation ◽  
Hormone Regulation ◽  
Breast Cancer Patients ◽  
Metabolic Remodeling

Estrogen receptor-positive (ER+) breast cancer patients are recommended hormone therapy as a primary adjuvant treatment after surgery. Aromatase inhibitors (AIs) are widely administered to ER+ breast cancer patients as estrogen blockers; however, their safety remains controversial. The use of letrozole, an AI, has been reported to cause adverse cardiovascular effects. We aimed to elucidate the effects of letrozole on the cardiovascular system. Female rats exposed to letrozole for four weeks showed metabolic changes, i.e., decreased fatty acid oxidation, increased glycolysis, and hypertrophy in the left ventricle. Although lipid oxidation yields more ATP than carbohydrate metabolism, the latter predominates in the heart under pathological conditions. Reduced lipid metabolism is attributed to reduced β-oxidation due to low circulating estrogen levels. In letrozole-treated rats, glycolysis levels were found to be increased in the heart. Furthermore, the levels of glycolytic enzymes were increased (in a high glucose medium) and the glycolytic rate was increased in vitro (H9c2 cells); the same was not true in the case of estrogen treatment. Reduced lipid metabolism and increased glycolysis can lower energy supply to the heart, resulting in predisposition to heart failure. These data suggest that a letrozole-induced cardiac metabolic remodeling, i.e., a shift from β-oxidation to glycolysis, may induce cardiac structural remodeling.

scholarly journals HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Hussain ◽  
Paromita Deb ◽  
Avisankar Chini ◽  
Monira Obaid ◽  
Arunoday Bhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Female Rats ◽  
Er Positive ◽  
Gene Regulatory ◽  
Cancer Tissues ◽  
Positive Breast Cancer

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

scholarly journals Trastuzumab-Modified Gold Nanoparticles Labeled with 211At as a Prospective Tool for Local Treatment of HER2-Positive Breast Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 632 ◽  
Author(s):  
Łucja Dziawer ◽  
Agnieszka Majkowska-Pilip ◽  
Damian Gaweł ◽  
Marlena Godlewska ◽  
Marek Pruszyński ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Local Treatment ◽  
Growth Factor Receptor ◽  
Dark Field ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Biological Studies ◽  
Positive Breast Cancer

Highly localized radiotherapy with radionuclides is a commonly used treatment modality for patients with unresectable solid tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This uses local intratumoral injection of 5-nm-diameter gold nanoparticles (AuNPs) labeled with an α-emitter (211At), modified with polyethylene glycol (PEG) chains and attached to HER2-specific monoclonal antibody (trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of gold for heavy halogens, the bioconjugate was labelled with 211At obtained by α irradiation of the bismuth target. The labeling yield of 211At was greater than 99%. 211At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that 211At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that 211At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the 211At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.

Triggered drug release from hybrid thermoresponsive nanoparticles using near infrared light

Nanomedicine ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. 219-234 ◽  
Author(s):  
Isabel Ortiz de Solorzano ◽  
Martin Prieto ◽  
Gracia Mendoza ◽  
Victor Sebastian ◽  
Manuel Arruebo
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Colloidal Stability ◽  
Near Infrared ◽  
Chemical Characterization ◽  
Infrared Light ◽  
Galvanic Replacement ◽  
Heating Efficiency ◽  
Hollow Gold Nanoparticles

Aim: Developing hybrid poly(N-isopropylacrylamide)-based nanogels decorated with plasmonic hollow gold nanoparticles for on-demand drug delivery and their physico-chemical characterization, bupivacaine loading and release ability upon light irradiation, and in vitro cell viability. Materials & methods: Hollow gold nanoparticles were prepared by galvanic replacement reaction; poly(N-isopropylacrylamide)-based nanogels were synthesized via precipitation polymerization and their electrostatic coupling was accomplished using poly(allylamine hydrochloride) as cationic polyelectrolyte linker. Results & conclusion: Colloidal stability of the resulted hybrid nanovectors was demonstrated under physiological conditions together with their fast response and excellent heating efficiency after light stimulation, indicating their potential use as triggered drug-delivery vectors. Moreover, their influence on cell metabolism and cell cycle under subcytotoxic doses were studied showing excellent cytocompatibility.

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