2025

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Chitosan-Functionalized Fluorescent Calcium Carbonate Nanoparticle Loaded with Methotrexate: Future Theranostics for Triple Negative Breast Cancer
(American Chemical Society, 2025) Rinki Verma; Md Zeyaullah; Virendra Pratap Singh; Preeti Suman Saxena; Biplob Koch; Manoj Kumar
Herein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines. The enhanced permeability and retention effect facilitated the accumulation of NPs, in tumor-bearing rats, as confirmed by in vivo fluorescence imaging. Treatment with @Calmat resulted in a marked reduction in pro-inflammatory cytokines, with levels of IL-6 (1225 ± 67 pg/mL), IL-1β (379 ± 69 pg/mL), and TNF-α (14.1 ± 2 pg/mL), in contrast to the diseased control group (IL-6: 2223 ± 99; IL-1β: 1632 ± 90; TNF-α: 40 ± 3 pg/mL). A similar trend was observed for liver and kidney function biomarkers. Mechanistic studies revealed that @Calmat treatment activates the Bax/Bcl-2 signaling pathway, leading to cell cycle arrest in the G1 phase and subsequent late-phase apoptosis. As a result, the tumor inhibition rate reached 88%, with 80% of treated rats surviving beyond 100 days. These findings highlight the strong potential of @Calmat as a dual-function theranostic agent for the management of TNBC. © 2025 American Chemical Society.
Heteroaryl-Capped Hydroxamic Acid Derivatives with Varied Linkers: Synthesis and Anticancer Evaluation with Various Apoptosis Analyses in Breast Cancer Cells, Including Docking, Simulation, DFT, and ADMET Studies
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Ekta Shirbhate; Biplob Koch; Vaibhav Singh; Akanksha Dubey; Haya Khader Ahmad Yasin; H. Rajak
Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI50 < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC50 of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. © 2025 by the authors.

2025

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