Sabyasachi Banerjee

Metal‐organic frameworks (MOFs) are materials that have recently emerged with the potential for various biomedical applications. Through engineering MOFs to contain various components and functionalities, they have progressed from porous materials to “smart” MOFs that can deliver payloads to cells, release the payloads in specific situations, perform certain therapies on the cells, and even perform diagnosis and therapy procedures simultaneously. This review aims to highlight the synergistic induction of ferroptosis through nanomedicine, immunotherapy, and targeted therapeutic agents for the treatment of breast and gastrointestinal (GI) malignancies. Nanotechnology‐based targeted delivery systems enhance the delivery of ferroptosis‐inducing agents to cancer cells while minimizing the toxicity of these agents to healthy cells. Additionally, immunotherapeutic agents enhance the immune response to cancer cells and sensitize them to ferroptotic cell death. Targeted therapeutic agents that act on the molecular regulators of ferroptosis, such as GPX4, System Xc ⁻ , NRF2, and iron metabolism, potentiate ferroptosis. The combination of these therapeutic strategies has the potential to reverse multidrug resistance, limit metastasis, and increase the efficacy of cancer therapy. Furthermore, this review discusses the current advances in and future perspectives on the development of combination therapies targeting ferroptotic cell death in cancer cells. The integration of nanomedicine, immunotherapy, and targeted therapeutic agents presents a highly promising new avenue for treating breast and gastrointestinal cancers.

Background: Daidzein, a secondary metabolite primarily obtained from soybean (Glycine max L.) and other legumes, has significant nutritional and pharmacological value. Chemically, daidzein is an isoflavone and plays a crucial role in the therapeutic amelioration of numerous disorders, including allergies, inflammation, diabetes, cardiovascular, and neurodegenerative diseases. Emerging preclinical evidence suggests potential antineoplastic activity of daidzein against various cancers. This current work aims to perform a critical evaluation of daidzein’s potential as an anticancer molecule with an in-depth understanding of its mechanisms of action. Methods: The data for this review were obtained from various sources, including PubMed, Scopus, and Web of Science. Results: Daidzein, as a pure phytochemical or in combination with other phytochemicals and anticancer drugs, has been reported to induce apoptotic and autophagic cell death, impeding cell growth, viability, proliferation, and angiogenesis, and arresting cell division at various phases in vitro. Various daidzein formulations also exhibited similar anticancer effects by immunomodulation and genetic alteration in the cancer cells. In vivo anticancer studies of daidzein also suggest modulation of several hallmark pathways, such as inhibition of nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, and rat sarcoma virus/rapidly accelerated fibrosarcoma. Conclusions: Irrespective of numerous promising preclinical studies, the absence of clinical studies provides a major challenge to establishing daidzein’s safety and efficacy in human cancers. Therefore, further advancements in clinical research of daidzein are vital for manifesting as an antineoplastic drug.

Organometallics, specifically ruthenium (Ru)-based complexes, have emerged as promising anticancer agents, offering controlled reactivity, electronic versatility, and tunable lipophilicity. The present work focuses on elucidating detailed anticancer cellular mechanisms of Ru(II)-gallate and Ru(II)-vanillate against MCF-7 breast and HepG2 liver cancer cells. Cell death pattern was assessed by flow cytometry, reactive oxygen species (ROS) level and mitochondrial membrane potential were measured by fluorescence assay, and the expression of key apoptosis-related proteins and genes were quantified by Western blot and quantitative reverse transcription polymerase chain reaction, respectively. Acute toxicity study was conducted in female Swiss albino mice. Mechanistic assays confirmed that both complexes substantially disrupted intracellular redox homeostasis, as evidenced by characteristic alterations in reduced glutathione/oxidized glutathione ratio indicative of reductive stress, leading to mitochondrial membrane depolarization, induced apoptotic cell death, suppressed anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), pro-caspase-3 levels (in HepG2 cells only), promoted mitochondrial cytochrome c release, elicited a concomitant rise in caspase-9, and upregulated Bcl-2-associated X-protein. The protein expression profile was further supplemented by analysis of important genes associated with apoptosis, such as BAX, BCL2, CASP3, and CASP9, performed using quantitative reverse transcription polymerase chain reaction. Acute oral toxicity study at a limit dose of 2000 mg/kg did not reveal adverse hematological, biochemical, or histopathological alterations in mice, indicating a non-toxic outcome under the tested conditions. This study revealed that Ru(II)-gallate and Ru(II)-vanillate induce mitochondria-mediated apoptosis driven by reductive stress, and exhibited strong in vivo tolerability, underscoring their potential as attractive contenders for cancer treatment pending further evaluation. Graphical Abstract

A very aggressive and deadly brain cancer, glioblastoma multiforme (GBM) poses formidable obstacles to effective therapy. Despite advancements in conventional therapies like surgery, chemotherapy, and radiation therapy, the prognosis for GBM patients remains poor, with limited survival outcomes. Nanotechnology is gaining popularity as a promising platform for managing GBM, offering targeted drug delivery, improved therapeutic efficacy, and reduced systemic toxicity. This review offers a comprehensive analysis of the current therapeutic approach for GBM using nanotechnology-based interventions. This study explored various nanocarrier (NC) systems like polymeric nanoparticles, liposomes, dendrimers, polymeric micelles, and mesoporous silica nanoparticles for improved precision as well as efficacy in encapsulating and delivering therapeutic agents to GBM tumors. Methods for improving drug delivery into GBM cells are described in this study, including novel delivery modalities such as convection-enhanced delivery, intranasal administration, magnetic hyperthermia, peptide-guided nanoparticles, and immune liposomes. It also explores the influence of diabetes and obesity on GBM prognosis and survival rates, suggesting that managing glucose levels and using metformin may improve patient outcomes. The discussion focuses on the advancements in nanotechnology-enabled GBM therapy, highlighting the challenges and opportunities in implementing these promising technologies in clinical practice. The study highlights the potential of nanotechnology and metabolic modulation in transforming GBM treatment strategies. To further understand how these factors impact GBM patients and develop innovative nanotechnology-based treatments for GBM and diabetes mellitus, more study is necessary.

The article ‘Ethnobotanical Documentation of Yerba Mate in Syria [https://www.qeios.com/read/DTCHU5]’ is quite interesting and much improved from the earlier version. The potential use of Yerba Mate should be placed in the introduction part, as the m...