Search Results (12)

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions. Full article

Despite improvements in therapeutic approaches like immunotherapy and gene therapy, cancer still remains a serious threat to world health due to its high incidence and mortality rates. Limitations of conventional therapy include suboptimal targeting, multidrug resistance, and systemic toxicity. A major challenge in current oncology therapies is the development of new delivery methods for antineoplastic drugs that act directly on target. One approach involves the complexation of antitumor drugs with cyclodextrins (CDs) and chitosan (CS) as an attempt to counteract their primary limitations: low water solubility and bioavailability, diminished in vitro and in vivo stability, and high dose-dependent toxicity. All those drawbacks may potentially exclude some therapeutic candidates from clinical trials, thus their integration into smart delivery systems or drug-targeting technologies must be implemented. We intended to overview new drug delivery systems based on chitosan or cyclodextrins with regard to the current diagnosis and cancer management. This narrative review encompasses full-length articles published in English between 2019 and 2025 (including online ahead of print versions) in PubMed-indexed journals, focusing on recent research on the encapsulation of diverse antitumor drugs within those nanosystems that exhibit responsiveness to various stimuli such as pH, redox potential, and folate receptor levels, thereby enhancing the release of bioactive compounds at tumor sites. The majority of the cited references focus on the most notable research, studies of novel applications, and scientific advancements in the field of nanostructures and functional materials employed in oncological therapies over the last six years. Certainly, there are additional stimuli with research potential that can facilitate the drug’s release upon activation, such as reactive oxygen species (ROS), various enzymes, ATP level, or hypoxia; however, our review exclusively addresses the aforementioned stimuli presented in a comprehensive manner. Full article

Enhancing the analytical performance of biosensors is a key factor in fabricating well-organized sensing platforms with high sensitivity. The main challenge in developing selective and sensitive biosensors is the lack of a sensing architecture that allows the detection of small biomolecules at low concentrations in crowded biological media. The functionality and stability of biosensors improve when the surface patterns are in a well-organized arrangement, and when biomaterials are present at a good density. It is common to use antibodies or aptamers as capture molecules for the target analyte, but they have limitations in terms of density and orientation when immobilized on sensor surfaces. Alternatively, simple non-toxic molecules such as folic acid (FA) can be used as recognition elements. They have the ability to construct nanostructures and produce sensing devices with good selectivity and sensitivity. In this study, the conjugation of FA to reduced graphene oxide (rGO) was prepared and then used to functionalize a glassy carbon electrochemical (GCE) electrode for the detection of breast cancer cells (MCF-7). The cyclic voltammetry (CV) technique was employed to characterize the electrochemical proficiency of the developed electrode for detecting MCF-7 cells. The rGO-FA nanobiocomposite demonstrated itself as a promising substrate, offering good electrochemical signals after capturing cancer cells in the range between 1 × 10³ and 1 × 10⁵ cells/mL. The CV results indicated the successful binding of the folate receptor overexpressed on the surface of the cell membrane in the MCF-7 cells to the rGO-FA-modified sensor. The simple design of rGO-FA/GCE showed good, reliable, and satisfactory performance, which may significantly contribute to the development of low-cost biosensors for future cancer diagnosis. Full article

There is an imminent need for novel strategies for the diagnosis and treatment of aggressive triple-negative breast cancer (TNBC). Cell-targeted multifunctional nanomaterials hold great potential, as they can combine precise early-stage diagnosis with local therapeutic delivery to specific cell types. In this study, we used mesoporous silica (MS)-coated gold nanobipyramids (MS-AuNBPs) for fluorescence imaging in the near-infrared (NIR) biological window, along with targeted TNBC treatment. Our MS-AuNBPs, acting partly as light amplification components, allow considerable metal-enhanced fluorescence for a NIR dye conjugated to their surfaces compared to the free dye. Fluorescence analysis confirms a significant increase in the dye’s modified quantum yield, indicating that MS-AuNBPs can considerably increase the brightness of low-quantum-yield NIR dyes. Meanwhile, we tested the chemotherapeutic efficacy of MS-AuNBPs in TNBC following the loading of doxorubicin within the MS pores and functionalization to target folate receptor alpha (FRα)-positive cells. We show that functionalized particles target FRα-positive cells with significant specificity and have a higher potency than free doxorubicin. Finally, we demonstrate that FRα-targeted particles induce stronger antitumor effects and prolong overall survival compared to the clinically applied non-targeted nanotherapy, Doxil. Together with their excellent biocompatibility measured in vitro, this study shows that MS-AuNBPs are promising tools to detect and treat TNBCs. Full article

Liver diseases cause approximately 2 million deaths per year worldwide and had an increasing incidence during the last decade. Risk factors for liver diseases include alcohol consumption, obesity, diabetes, the intake of hepatotoxic substances like aflatoxin, viral infection, and genetic determinants. Liver cancer is the sixth most prevalent cancer and the third in mortality (second in males). The low survival rate (less than 20% in 5 years) is partially explained by the late diagnosis, which remarks the need for new early molecular biomarkers. One-carbon metabolism integrates folate and methionine cycles and participates in essential cell processes such as redox homeostasis maintenance and the regulation of methylation reactions through the production of intermediate metabolites such as cysteine and S-Adenosylmethionine. One-carbon metabolism has a tissue specific configuration, and in the liver, the participating enzymes are abundantly expressed—a requirement to maintain hepatocyte differentiation. Targeted proteomics studies have revealed significant differences in hepatocellular carcinoma and cirrhosis, suggesting that monitoring one-carbon metabolism enzymes can be useful for stratification of liver disease patients and to develop precision medicine strategies for their clinical management. Here, reprogramming of one-carbon metabolism in liver diseases is described and the role of mass spectrometry to follow-up these alterations is discussed. Full article

Histone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that are involved in gene transcription and regulation, cell proliferation, differentiation, migration, and death, as well as angiogenesis. Particularly, disorders of the HDACs expression are linked to the development of many types of cancer and neurodegenerative diseases, making them interesting molecular targets for the design of new efficient drugs and imaging agents that facilitate an early diagnosis of these diseases. Thus, their selective inhibition or degradation are the basis for new therapies. This is supported by the fact that many HDAC inhibitors (HDACis) are currently under clinical research for cancer therapy, and the Food and Drug Administration (FDA) has already approved some of them. In this review, we will focus on the recent advances and latest discoveries of innovative strategies in the development and applications of compounds that demonstrate inhibitory or degradation activity against HDACs, such as PROteolysis-TArgeting Chimeras (PROTACs), tumor-targeted HDACis (e.g., folate conjugates and nanoparticles), and imaging probes (positron emission tomography (PET) and fluorescent ligands). Full article

Globally, breast cancer (BC) poses a serious public health risk. The disease exhibits a complex heterogeneous etiology and is associated with a glycolytic and oxidative phosphorylation (OXPHOS) metabolic reprogramming phenotype, which fuels proliferation and progression. Due to the late manifestation of symptoms, rigorous treatment regimens are required following diagnosis. Existing treatments are limited by a lack of specificity, systemic toxicity, temporary remission, and radio-resistance in BC. In this study, we have developed CD44 and folate receptor-targeting multi-functional dual drug-loaded nanoparticles. This composed of hyaluronic acid (HA) and folic acid (FA) conjugated to a 2-deoxy glucose (2DG) shell linked to a layer of dichloroacetate (DCA) and a magnesium oxide (MgO) core (2DG@DCA@MgO; DDM) to enhance the localized chemo-radiotherapy for effective BC treatment. The physicochemical properties of nanoparticles including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy were thoroughly examined. Mechanistically, we identified multiple component signaling pathways as important regulators of BC metabolism and mediators for the inhibitory effects elicited by DDM. Nanoparticles exhibited sustained DDM release properties in a bio-relevant media, which was responsive to the acidic pH enabling eligibility to the control of drug release from nanoparticles. DDM-loaded and HA–FA-functionalized nanoparticles exhibited increased selectivity and uptake by BC cells. Cell-based assays revealed that the functionalized DDM significantly suppressed cancer cell growth and improved radiotherapy (RT) through inducing cell cycle arrest, enhancing apoptosis, and modulating glycolytic and OXPHOS pathways. By highlighting DDM mechanisms as an antitumor and radio-sensitizing reagent, our data suggest that glycolytic and OXPHOS pathway modulation occurs via the PI3K/AKT/mTOR/NF-κB/VEGF_low and P53_high signaling pathway. In conclusion, the multi-functionalized DDM opposed tumor-associated metabolic reprogramming via multiple signaling pathways in BC cells as a promising targeted metabolic approach. Full article

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA₂-dPEG-DOX₂). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA₂-dPEG-DOX₂ would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation. Full article

The detection of cancer biomarkers in the early stages could prevent cancer-related deaths significantly. Nanomaterials combined with biomolecules are extensively used in drug delivery, imaging, and sensing applications by targeting the overexpressed cancer proteins such as folate receptors (FRs) to control the disease by providing earlier treatments. In this investigation, biocompatible reduced graphene oxide (rGO) nanosheets combined with folic acid (FA)-a vitamin with high bioaffinity to FRs-is utilized to develop an electrochemical sensor for cancer detection. To mimic the cancer cell environment, FR-β protein is used to evaluate the response of the rGO-FA sensor. The formation of the rGO-FA nanocomposite was confirmed through various characterization techniques. A glassy carbon (GC) electrode was then modified with the obtained rGO-FA and analyzed via differential pulse voltammetry (DPV) for its specific detection towards FRs. Using the DPV technique, the rGO-FA-modified electrode exhibited a limit of detection (LOD) of 1.69 pM, determined in a linear concentration range from 6 to 100 pM. This excellent electrochemical performance towards FRs detection could provide a significant contribution towards future cancer diagnosis. Moreover, the rGO-FA sensing platform also showed excellent specificity and reliability when tested against similar interfering biomolecules. This rGO-FA sensor offers a great promise to the future medical industry through its highly sensitive detection towards FRs in a fast, reliable, and economical way. Full article

Lung cancer is among the most prevalent and leading causes of death worldwide. The major reason for high mortality is the late diagnosis of the disease, and in most cases, lung cancer is diagnosed at fourth stage in which the cancer has metastasized to almost all vital organs. The other reason for higher mortality is the uptake of the chemotherapeutic agents by the healthy cells, which in turn increases the chances of cytotoxicity to the healthy body cells. The complex pathophysiology of lung cancer provides various pathways to target the cancerous cells. In this regard, upregulated onco-receptors on the cell surface of tumor including epidermal growth factor receptor (EGFR), integrins, transferrin receptor (TFR), folate receptor (FR), cluster of differentiation 44 (CD44) receptor, etc. could be exploited for the inhibition of pathways and tumor-specific drug targeting. Further, cancer borne immunological targets like T-lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells could serve as a target site to modulate tumor activity through targeting various surface-expressed receptors or interfering with immune cell-specific pathways. Hence, novel approaches are required for both the diagnosis and treatment of lung cancers. In this context, several researchers have employed various targeted delivery approaches to overcome the problems allied with the conventional diagnosis of and therapy methods used against lung cancer. Nanoparticles are cell nonspecific in biological systems, and may cause unwanted deleterious effects in the body. Therefore, nanodrug delivery systems (NDDSs) need further advancement to overcome the problem of toxicity in the treatment of lung cancer. Moreover, the route of nanomedicines’ delivery to lungs plays a vital role in localizing the drug concentration to target the lung cancer. Surface-modified nanoparticles and hybrid nanoparticles have a wide range of applications in the field of theranostics. This cross-disciplinary review summarizes the current knowledge of the pathways implicated in the different classes of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. Furthermore, it focuses specifically on the significance and emerging role of surface functionalized and hybrid nanomaterials as drug delivery systems through citing recent examples targeted at lung cancer treatment. Full article

Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted, efficient, cost-effective therapy, exhibiting a significant need for novel approaches to address these concerns. For this purpose, nanotechnology has revolutionized the field of medicine with versatile potential capabilities for both the diagnosis, as well as the treatment, of retinoblastoma via the targeted and controlled delivery of anticancer drugs via binding to the overexpressed retinoblastoma gene. Nanotechnology has also generated massive advancements in the treatment of retinoblastoma based on the use of surface-tailored multi-functionalized nanocarriers; overexpressed receptor-based nanocarriers ligands (folate, galactose, and hyaluronic acid); lipid-based nanocarriers; and metallic nanocarriers. These nanocarriers seem to benchmark in mitigating a plethora of malignant retinoblastoma via targeted delivery at a specified site, resulting in programmed apoptosis in cancer cells. The effectiveness of these nanoplatforms in diagnosing and treating intraocular cancers such as retinoblastoma has not been properly discussed, despite the increasing significance of nanomedicine in cancer management. This article reviewed the recent milestones and future development areas in the field of intraocular drug delivery and diagnostic platforms focused on nanotechnology. Full article

Ovarian cancer is the main cause of death from gynecological cancer, with its poor prognosis mainly related to late diagnosis and chemoresistance (acquired or intrinsic) to conventional alkylating and reactive oxygen species (ROS)-generating drugs. We and others reported that the availability of cysteine and glutathione (GSH) impacts the mechanisms of resistance to carboplatin in ovarian cancer. Different players in cysteine metabolism can be crucial in chemoresistance, such as the cystine/glutamate antiporter system Xc (xCT) and the H₂S-synthesizing enzyme cystathionine β-synthase (CBS) in the pathway of cysteine catabolism. We hypothesized that, by disrupting cysteine metabolic flux, chemoresistance would be reverted. Since the xCT transporter is also able to take up selenium, we used selenium-containing chrysin (SeChry) as a plausible competitive inhibitor of xCT. For that, we tested the effects of SeChry on three different ovarian cancer cell lines (ES2, OVCAR3, and OVCAR8) and in two non-malignant cell lines (HaCaT and HK2). Results showed that, in addition to being highly cytotoxic, SeChry does not affect the uptake of cysteine, although it increases GSH depletion, indicating that SeChry might induce oxidative stress. However, enzymatic assays revealed an inhibitory effect of SeChry toward CBS, thus preventing production of the antioxidant H₂S. Notably, our data showed that SeChry and folate-targeted polyurea dendrimer generation four (SeChry@PURE_G4-FA) nanoparticles increased the specificity for SeChry delivery to ovarian cancer cells, reducing significantly the toxicity against non-malignant cells. Collectively, our data support SeChry@PURE_G4-FA nanoparticles as a targeted strategy to improve ovarian cancer treatment, where GSH depletion and CBS inhibition underlie SeChry cytotoxicity. Full article