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Öğe Amine-functionalized mesoporous silica nanoparticles decorated by silver nanoparticles for delivery of doxorubicin in breast and cervical cancer cells(Elsevier, 2024) Ghobadi, Melika; Salehi, Saeideh; Ardestani, Mohammad Taha Salmanifard; Mousavi-Khattat, Mohammad; Shakeran, Zahra; Khosravi, Arezoo; Cordani, Marco; Zarrabi, AliNanocarriers have demonstrated promising potential in the delivery of various anticancer drugs and in improving the efficiency of the treatment. In this study, silver nanoparticles (AgNPs) were green-synthesized using the extracts of different parts of the pomegranate plant, including the peel, flower petals, and calyx. To obtain the most efficient extract used for the green synthesis of AgNPs, all three types of synthesized nanoparticles were characterized. Then, (3-Aminopropyl) triethoxysilane-functionalized mesoporous silica nanoparticles (MSNs-APTES) decorated with AgNPs were fabricated via a one-pot green-synthesis method. AgNPs were directly coated on the surface of MSNs-APTES by adding pomegranate extract enriched with a source of reducing agent leading to converting the silver ion to AgNPs. The MSN-APTES-AgNPs (MSNs-AgNPs) have been thoroughly characterized using nanoparticle characterization techniques. In addition, DNA cleavage and hemolysis activities of the synthesized nanoparticles were analyzed, confirming the biocompatibility of synthesized nanoparticles. The Doxorubicin (DOX, as a breast/cervical anti-cancer drug) loading (42.8%) and release profiles were investigated via UV-visible spectroscopy. The fibroblast, breast cancer, and cervical cancer cells' viability against DOX-loaded nanoparticles were also studied. The results of this high drug loading, uniform shape, and small functionalized nanoparticles demonstrated its great potential for breast and cervical cancer management.Öğe Biotin-functionalized nanoparticles: an overview of recent trends in cancer detection(Royal soc chemistry, 2024) Fathi-karkan, Sonia; Sargazi, Saman; Shojaei, Shirin; Farasati Far, Bahareh; Mirinejad, Shekoufeh; Cordani, Marco; Khosravi, Arezoo; Zarrabi, Ali; Ghavami, SaeidElectrochemical bio-sensing is a potent and efficient method for converting various biological recognition events into voltage, current, and impedance electrical signals. Biochemical sensors are now a common part of medical applications, such as detecting blood glucose levels, detecting food pathogens, and detecting specific cancers. As an exciting feature, bio-affinity couples, such as proteins with aptamers, ligands, paired nucleotides, and antibodies with antigens, are commonly used as bio-sensitive elements in electrochemical biosensors. Biotin-avidin interactions have been utilized for various purposes in recent years, such as targeting drugs, diagnosing clinically, labeling immunologically, biotechnology, biomedical engineering, and separating or purifying biomolecular compounds. The interaction between biotin and avidin is widely regarded as one of the most robust and reliable noncovalent interactions due to its high bi-affinity and ability to remain selective and accurate under various reaction conditions and bio-molecular attachments. More recently, there have been numerous attempts to develop electrochemical sensors to sense circulating cancer cells and the measurement of intracellular levels of protein thiols, formaldehyde, vitamin-targeted polymers, huwentoxin-I, anti-human antibodies, and a variety of tumor markers (including alpha-fetoprotein, epidermal growth factor receptor, prostate-specific Ag, carcinoembryonic Ag, cancer antigen 125, cancer antigen 15-3, etc.). Still, the non-specific binding of biotin to endogenous biotin-binding proteins present in biological samples can result in false-positive signals and hinder the accurate detection of cancer biomarkers. This review summarizes various categories of biotin-functional nanoparticles designed to detect such biomarkers and highlights some challenges in using them as diagnostic tools. Biotin-functionalized nanoparticles enhance cancer detection by targeting biotin receptors, which are overexpressed on cancer cells. This targeted approach improves imaging accuracy and efficacy in identifying cancerous tissues.Öğe Carbon-based nanozymes for cancer therapy and diagnosis: a review(Elsevier b.v., 2025) Cordani, Marco; Fernández-Lucas, Jesús; Khosravi, Arezoo; Zare, Ehsan Nazarzadeh; Makvandi, Pooyan; Zarrabi, Ali; Iravani, SiavashCarbon-based nanozymes (CNs) have emerged as a significant innovation in targeted cancer therapy, demonstrating great potential for advancing cancer diagnosis and treatment. With exceptional catalytic properties, remarkable biocompatibility, and the ability to precisely target cancer cells, CNs provide a promising avenue for the development of novel oncological therapies. By functionalizing their surfaces with targeting ligands, such as antibodies or peptides, CNs can specifically recognize and bind to cancer cells. This targeted approach ensures that therapeutic agents are delivered directly to the tumor site, minimizing off-target effects, and reducing systemic toxicity. Additionally, the enzyme-like activities of CNs, when combined with conventional therapies such as chemotherapeutics, photothermal therapy, and photodynamic therapy, or other modalities can enhance therapeutic outcomes. Integrating CNs into clinical practice could significantly improve therapeutic efficacy, reduce probable side effects, enhance patient outcomes, and drive a shift towards more personalized cancer care. Besides, CNs can also be employed in biosensors and diagnostic nanomaterials, enabling rapid, selective, and highly accurate detection of specific biomarkers. Their versatile functionalities open new avenues for refining imaging techniques, ultimately contributing to early diagnosis and better clinical decision-making. This review consolidates recent studies exploring CNs in cancer targeting, highlighting both their diagnostic and therapeutic potential in oncology.Öğe A comparison study between doxorubicin and curcumin co-administration and co-loading in a smart niosomal formulation for MCF-7 breast cancer therapy(Elsevier, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Nasri, Negar; Cordani, Marco; Zarrabi, AliChemotherapy agents often exhibit limited effectiveness due to their fast elimination from the body and nontargeted delivery. Emerging nanomaterials as drug delivery carriers open new expectancy to overcome these limitations in current chemotherapeutic treatments. In this study, we introduce and evaluate a smart pHresponsive niosomal formulation capable of delivering Doxorubicin (DOX) and Curcumin (CUR) in both individually and co-loaded forms. In particular, drug-loaded niosomes were prepared using thin-film hydration method and then characterized via different physicochemical analyses. The pH responsivity of the carrier was assessed by performing a drug release study in three different pH conditions (4, 6.5, and 7.4). Finally, the anticancer efficacy of the therapeutic compounds was evaluated through the MTT assay. Our results showed spherical particles with a size of about 200 nm and -2 mV surface charge. Encapsulation efficiency (EE%) of the nanocarrier was about 77.06 % and 79.08 % for DOX and CUR, respectively. The release study confirmed the pH responsivity of the carrier. The MTT assay results revealed about 39 % and 43 % of cell deaths after treatment with cur-loaded and dox-loaded niosomes, which increased to 74 % and 79 % after co-administration and coloading forms of drugs, respectively, exhibiting increased anticancer efficacy by selectively delivering DOX and CUR individually or in combination. Overall, these findings suggest that our nanoformulation holds the potential as a targeted and highly effective approach for cancer management and therapy, overcoming the limitations of conventional chemotherapy drugs.Öğe Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression(Mdpi, 2024) Strippoli, Raffaele; Niayesh-Mehr, Reyhaneh; Adelipour, Maryam; Khosravi, Arezoo; Cordani, Marco; Zarrabi, Ali; Allameh, AbdolamirSimple Summary This manuscript focuses on the complex relationships between autophagy and epithelial mesenchymal transition (EMT) in cancer. Autophagy, a cellular degradation process, and EMT, a mechanism where epithelial cells acquire mesenchymal features, both play significant roles in cancer development. This review aims to explore how these processes interact, particularly how autophagy impacts cancer cell fate during EMT. The findings from this study are expected to contribute to a better understanding of cancer biology and could potentially impact cancer treatment strategies, as both autophagy and EMT are considered targets for therapy.Abstract Epithelial Mesenchymal Transition (EMT) is a dedifferentiation process implicated in many physio-pathological conditions including tumor transformation. EMT is regulated by several extracellular mediators and under certain conditions it can be reversible. Autophagy is a conserved catabolic process in which intracellular components such as protein/DNA aggregates and abnormal organelles are degraded in specific lysosomes. In cancer, autophagy plays a controversial role, acting in different conditions as both a tumor suppressor and a tumor-promoting mechanism. Experimental evidence shows that deep interrelations exist between EMT and autophagy-related pathways. Although this interplay has already been analyzed in previous studies, understanding mechanisms and the translational implications of autophagy/EMT need further study. The role of autophagy in EMT is not limited to morphological changes, but activation of autophagy could be important to DNA repair/damage system, cell adhesion molecules, and cell proliferation and differentiation processes. Based on this, both autophagy and EMT and related pathways are now considered as targets for cancer therapy. In this review article, the contribution of autophagy to EMT and progression of cancer is discussed. This article also describes the multiple connections between EMT and autophagy and their implication in cancer treatment.Öğe Metal-based nanoparticles in cancer therapy: Exploring photodynamic therapy and its interplay with regulated cell death pathways(Elsevier, 2024) Pashootan, Parya; Saadati, Fatemeh; Fahimi, Hossein; Rahmati, Marveh; Strippoli, Raffaele; Zarrabi, Ali; Cordani, MarcoPhotodynamic therapy (PDT) represents a non-invasive treatment strategy currently utilized in the clinical management of selected cancers and infections. This technique is predicated on the administration of a photo-sensitizer (PS) and subsequent irradiation with light of specific wavelengths, thereby generating reactive oxygen species (ROS) within targeted cells. The cellular effects of PDT are dependent on both the localization of the PS and the severity of ROS challenge, potentially leading to the stimulation of various cell death modalities. For many years, the concept of regulated cell death (RCD) triggered by photodynamic reactions predominantly encompassed apoptosis, necrosis, and autophagy. However, in recent decades, further explorations have unveiled additional cell death modalities, such as necroptosis, ferroptosis, cuproptosis, pyroptosis, parthanatos, and immunogenic cell death (ICD), which helps to achieve tumor cell elimination. Recently, nanoparticles (NPs) have demonstrated substantial advantages over traditional PSs and become important components of PDT, due to their improved physicochemical properties, such as enhanced solubility and superior specificity for targeted cells. This review aims to summarize recent advancements in the applications of different metal-based NPs as PSs or delivery systems for optimized PDT in cancer treatment. Furthermore, it mechanistically highlights the contribution of RCD pathways during PDT with metal NPs and how these forms of cell death can improve specific PDT regimens in cancer therapy.Öğe MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells(Elsevier B.V., 2024) Seydi, Homeyra; Nouri, Kosar; Shokouhian, Bahare; Piryaei, Abbas; Hassan, Moustapha; Cordani, Marco; Zarrabi, Ali; Shekari, Faezeh; Vosough, MassoudBackground: In spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. Method: Human Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. Results: EV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway. © 2024 Elsevier B.V.Öğe Preparation and characterization of PBS (polybutylene succinate) nanoparticles containing cannabidiol (CBD) for anticancer application(Elsevier, 2024) Freire, Natalia Freitas; Cordani, Marco; Aparicio-Blanco, Juan; Sanchez, Ana Isabel Fraguas; Dutra, Luciana; Pinto, Martina C. C.; Zarrabi, Ali; Pinto, Jose Carlos; Velasco, Guillermo; Fialho, RosanaCannabidiol (CBD), a major constituent of Cannabis sativa, has demonstrated a broad range of therapeutic properties in human studies. Notably, CBD has shown anticancer activity in preclinical cancer models. However, its low water solubility poses challenges for bioavailability, necessitating the development of drug delivery systems to enhance its efficacy. This study aimed to create CBD-loaded Poly (butylene succinate) (PBS) nanoparticles and evaluate their effectiveness in in vitro cancer models. The nanoparticles, with an average size of 175 nm, were produced using a modified double emulsion/solvent evaporation technique. The release profile of CBD from the nanoparticles exhibited an initial rapid release followed by a slower sustained release. Cytotoxicity assays demonstrated that the CBD-PBS nanoparticles retained the anticancer effects of free CBD, selectively reducing the viability of cancer cell lines without affecting non -transformed fibroblasts. Additionally, the nanoformulation modulated key cellular pathways, as indicated by decreased AKT phosphorylation and increased LC3-II levels, suggesting that the encapsulated CBD preserved its ability to induce autophagy-mediated cell death in cancer cells. The nanoformulation also effectively inhibited cell migration in highly invasive prostate cancer cells, mirroring the effects of free CBD, while not impacting the migration of non -tumoral fibroblasts. These results underscore the therapeutic potential of this CBD nanoformulation, setting the stage for further in vivo investigations.Öğe The role of glycolysis in tumorigenesis: from biological aspects to therapeutic opportunities(Elsevier inc., 2024) Cordani, Marco; Michetti, Federica; Zarrabi, Ali; Zarepour, Atefeh; Rumio, Cristiano; Strippoli, Raffaele; Marcucci, FabrizioGlycolytic metabolism generates energy and intermediates for biomass production. Tumor-associated glycolysis is upregulated compared to normal tissues in response to tumor cell-autonomous or non-autonomous stimuli. The consequences of this upregulation are twofold. First, the metabolic effects of glycolysis become predominant over those mediated by oxidative metabolism. Second, overexpressed components of the glycolytic pathway (i.e. enzymes or metabolites) acquire new functions unrelated to their metabolic effects and which are referred to as "moonlighting" functions. These functions include induction of mutations and other tumor-initiating events, effects on cancer stem cells, induction of increased expression and/or activity of oncoproteins, epigenetic and transcriptional modifications, bypassing of senescence and induction of proliferation, promotion of DNA damage repair and prevention of DNA damage, antiapoptotic effects, inhibition of drug influx or increase of drug efflux. Upregulated metabolic functions and acquisition of new, non-metabolic functions lead to biological effects that support tumorigenesis: promotion of tumor initiation, stimulation of tumor cell proliferation and primary tumor growth, induction of epithelial-mesenchymal transition, autophagy and metastasis, immunosuppressive effects, induction of drug resistance and effects on tumor accessory cells. These effects have negative consequences on the prognosis of tumor patients. On these grounds, it does not come to surprise that tumor-associated glycolysis has become a target of interest in antitumor drug discovery. So far, however, clinical results with glycolysis inhibitors have fallen short of expectations. In this review we propose approaches that may allow to bypass some of the difficulties that have been encountered so far with the therapeutic use of glycolysis inhibitors.Öğe Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies(Bmc, 2024) Ambrosini, Giulia; Cordani, Marco; Zarrabi, Ali; Alcon-Rodriguez, Sergio; Sainz, Rosa M.; Velasco, Guillermo; Gonzalez-Menendez, PedroProstate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies.
