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Item Lineage of lipid-based endosomal escape in cytosolic delivery to cancer: insight into an unprecedented approach(Elsevier, 2025-12) Jain, AnkitEndosomal sequestration of lipid-based systems constitutes a significant limitation that undermines the efficient intracellular delivery of therapeutics in cancer treatment. Upon administration, the intracellular fate of drug or gene constructs within lipid-based delivery systems is influenced by various factors, including p-glycoprotein-mediated efflux and lysosomal degradation, which impede sufficient therapeutic agents from reaching their intended targets. This review exhaustively discusses lipids (properties of lipids and role of pKa) and various lipid-based delivery systems facilitating the endosomal escape for cancer treatment. All aspects, such as endosomal sequestration, methods to promote endosomal escape, a mechanistic overview of endosomal escape, detection of endosomal escape, the application potential of lipid-based systems for cancer treatment, and safety of lipid-based systems, were covered in this manuscript. Existing reviews on endosomal escape have accounted for the various mechanisms,. Still, this review paper also furnishes the role of pKa and applications of molecular dynamic simulation in lipid-based drug delivery, and safety concernsof lipid-based nanosystems. This review discussed the influence of material properties on the endosomal escape of therapeutic agents.Item Proteomics analysis in urinary bladder cancer patients identifies urinary SOD2 as a predictive marker of recurrence(2021-12) Dubey, Uma S.Early non-invasive detection of tumor is an urgent clinical need for managing urothelial bladder cancer. Cystoscopy and cytology are the current standards for diagnosis of recurrence, but are limited by low sensitivity. Quantitative proteomics tool was employed to identify important deregulated molecules in bladder cancer tissues and validated using Western blot and immunohistochemistry analysis. A set of 1137 proteins were identified in four paired bladder cancer patients. Among these, 64 proteins were deregulated in all cases among which 9 were commonly up-regulated. The Ingenuity Pathway Analysis (IPA) generated top 11 Networks in which three commonly upregulated (SERPING1, SOD2 and HSPB6) proteins were involved and selected for further validation. Tissue expression of SOD2, SERPING1 and HSPB6 monitored in an independent sample set (n=18) by immuno-histochemical analysis showed similar profile. Western blot analysis of these proteins in urine of bladder cancer (n=26) and healthy subjects (n=10) showed a specificity and sensitivity of >80% for SOD2 and so was selected for further validation in a separate set (n=150) by ELISA. Significant elevation in urinary SOD2 level was found in urothelial bladder cancer patients compared to healthy controls and in recurrent cases compared to primary (p-value<0.001). Kaplan Meier survival analysis showed urinary SOD2 concentration >2,100 pg/ml was significantly associated with poorer survival.Cumulative survival of patient with low SOD2 concentration was 34.4% compared to 18.9% in patient with high SOD2 at 24 months (p=0.025). The study identifies SOD2 as a non-invasive biomarker which may help to extend the period between cystoscopies during follow-up.Item Metal-free, visible-light-mediated synthesis of tetracyclic benzimidazole: regioselective c–h functionalization with in vitro and computational study of anti-breast cancer compounds(ACS, 2025-02) Murugesan, Sankaranarayanan; Mukherjee, SudeshnaGlobally, breast cancer is the leading cause of mortality. Within the field of antibreast cancer drug design by several compound docking studies, eight new N-containing nonsteroid tetracyclic derivatives have been synthesized via regioselective intramolecular C–H functionalization by visible light. The adopted methodology is highly efficient, green, and sustainable to unload a new pathway with excellent yield. It offers a rapid, low-cost, catalyst-free method for creating physiologically active molecules from easily accessible substrates. The synthesized substances were described using spectroscopic methods like HRMS, 1HNMR, 13CNMR, and XRD analysis. This study explores the cytotoxic potential of novel compounds against human MCF-7 breast cancer cells. This study includes in vitro experiments to assess the effect of our compounds on cells. These experiments include cytotoxicity assessment by cell cycle, apoptosis, MTT test analysis by flow cytometry, reactive oxygen species (ROS) production assessment, etc. Among the novel compounds, compound 2e exhibited the most potent cytotoxic activity, with an inhibitory concentration (IC50) of 40 nM, surpassing the efficacy of established drugs such as exemestane (IC50 24.97 micromolar) and tamoxifen (IC50 5.45 μM). Compound 2e also significantly induced apoptosis and cell cycle arrest in the G1 phase, increasing the apoptotic cell population to 65.97%. Additionally, the compound led to a marked rise in the level of ROS generation, implicating oxidative stress in its mechanism of action. Molecular docking and dynamic simulation further supported the vigorous anticancer activity of compound 2e, demonstrating its promise as an effective breast cancer treatment.Item Design, synthesis, and biological evaluation of novel quinazolin-4(3h)-one-based histone deacetylase 6 (hdac6) inhibitors for anticancer activity(MDPI, 2023-07) Murugesan, SankaranarayananA series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on novel quinazoline-4-(3H)-one as the cap group and benzhydroxamic acid as the linker and metal-binding group. A total of 19 novel quinazoline-4-(3H)-one analogues (5a–5s) were obtained. The structures of the target compounds were characterized using 1H-NMR, 13C-NMR, LC–MS, and elemental analyses. Characterized compounds were screened for inhibition against HDAC8 class I, HDAC4 class IIa, and HDAC6 class IIb. Among the compounds tested, 5b proved to be the most potent and selective inhibitor of HDAC6 with an IC50 value 150 nM. Some of these compounds showed potent antiproliferative activity in several tumor cell lines (HCT116, MCF7, and B16). Amongst all the compounds tested for their anticancer effect against cancer cell lines, 5c emerged to be most active against the MCF-7 line with an IC50 of 13.7 μM; it exhibited cell-cycle arrest in the G2 phase, as well as promoted apoptosis. Additionally, we noted a significant reduction in the colony-forming capability of cancer cells in the presence of 5c. At the intracellular level, selective inhibition of HDAC6 was enumerated by monitoring the acetylation of α-tubulin with a limited effect on acetyl-H3. Importantly, the obtained results suggested a potent effect of 5c at sub-micromolar concentrations as compared to the other molecules as HDAC6 inhibitors in vitro.Item Pharmacoinformatics-based prediction of checkpoint kinase-1 inhibitors from momordica charantia linn. for cancer(Elsevier, 2025-04) Murugesan, SankaranarayananCheckpoint kinase 1 (Chk-1), a serine/threonine kinase family protein, is an emerging target in cancer research owing to its crucial role in cell cycle arrest. Therefore, we aimed to predict potential Chk-1 inhibitors from Momordica charantia Linn., using high-throughput molecular docking. We used a graph theoretical network approach to determine the target protein, Chk-1. Among 86 compounds identified from M. charantia L., five molecules such as α-spinasterol (-9.7 kcal × mol−1), stigmasterol (-9.6 kcal × mol−1), stigmasta-7,22,25-trienol (-9.5 kcal × mol−1), campesterol (-9.5 kcal × mol−1), and stigmasta-7,25-dien-3beta-ol (-9.5 kcal × mol−1) and standard drug CCT245737 (-8.3 kcal × mol-1) displayed highest binding affinity with Chk-1. Besides, pharmacokinetic studies have demonstrated the non-toxic and drug-like properties of these compounds. Furthermore, molecular dynamics (MD) simulation studies confirmed the strong intermolecular interactions and stability of the compounds with Chk-1. The estimation of binding free-energy derived from molecular docking was fully recognized by the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) produced from the MD simulation paths. Altogether, these five compounds may serve as effective inhibitors of Chk-1, thereby could be used to develop new medications for cancer treatment.Item Downregulation of microRNA-29b in cancer and fibrosis: molecular insights and clinical implications(Elsevier, 2024-11) Chitkara, DeepakMicroRNA-29b (miR-29b) is known for its therapeutic potential as an antifibrotic and anticancer agent. In fibrotic conditions, miR-29b inhibits fibrogenesis by downregulating crucial regulators such as collagens, extracellular matrix proteins and the transforming growth factor-β pathway. Similarly, in cancer, it acts as a tumor suppressor by downregulating various oncogenes and signaling pathways involved in cancer progression, such as Wnt–β-catenin, p38–mitogen-activated protein kinase and nuclear factor-κB. However, the upregulation of these pathways suppresses miR-29b, contributing to fibrosis and cancer development. Preclinical research and clinical trials have shown that delivering exogenous miR-29b mimics can restore its expression, attenuating tumorigenesis and fibrogenesis. This review discusses miR-29b’s potential and its possible therapeutic development for cancer and fibrotic disorders.Item Liposomal delivery system(Springer, 2022-03) Jain, AnkitLiposomes are biodegradable and biocompatible lipid bilayer vesicles that are employed as potential carriers for the delivery of drugs to the desired site. It is used for the delivery of both hydrophobic and hydrophilic drugs. Because of the variability in composition and structural properties, liposomes are widely used in biomedical applications. Recently, multifunctional liposomes have been reported for tumor targeting. Liposomal delivery systems are modified in several ways according to their applications. Ligand-modified liposomes are used for targeted drug delivery. Stimuli-sensitive liposomes are used to obtain the trigger drug release at the site of action. Theranostic liposomal systems are used for diagnosis as well as therapeutic purposes. This chapter highlights the basics and classification of liposomes. It encompasses a detailed account of ligand targeted liposomes (such as folate, transferrin, mannose, hyaluronic acid, and asialoglycoprotein), and stimuli-sensitive liposomes (such as pH, temperature, magnetic field, hypoxia, and photo-triggered) for tumor targeting. It also includes some marketed liposomal products used for cancer treatmentItem A glimpse of biomedical application potential of biodegradable polymers for anticancer drug delivery(Elsevier, 2022) Jain, AnkitThe major anticancer drugs used for cancer therapy show nonspecificity, wide biodistribution, a short half-life, a low concentration in tumor tissue, and systemic toxicity. The biodegradable polymer can be used as an approach that acts as a drug carrier, offering a targeted drug delivery and increasing the drug payload to the tumor tissues and cells. It also enhances biocompatibility, provides prolonged release of the drug allowing controlled and sustained release, and minimizes systemic toxicity. This chapter focuses on targeted drug delivery through a stimuli-responsive drug carrier that releases its payload at the specified site and on demand in response to an external stimulus. It also emphasizes various applications of biodegradable polymers in breast cancer, lung cancer, colon cancer, and uterine cancer with special emphasis on theranostic applications.Item Theranostic nanocarriers for cancer applications(CRC Press, 2024) Jain, AnkitCancer is one of the deadly diseases with serious health concerns that needed novel therapeutic solutions. For an effective and successful treatment approach, upgraded and advanced diagnostics as well as therapeutic techniques are required. Currently, research and development in this area are in great demand in nanoscience and nanotechnology. They promise to offer innovative and more effective approaches to cancer for its early diagnosis, imaging, and therapy. An emerging and growing trend in this direction is theranostics. It deals with both the diagnosis and therapeutic approach to cancers conjointly. Its prime objectives are to eliminate multi-step processes and reduce delays in cancer treatment. It offers many advantages, such as better-quality diagnosis, cancer-specific drug delivery, and minimization of toxic effects to healthy tissues. Many theranostic nanocarriers like nanoparticles, quantum dots, carbon nanotubes, nanofibers, nanoshells, liposomes, dendrimers, and micelles can be used efficiently for the effective treatment of cancer. This chapter examines several theranostic nanocarriers and their applications for effective cancer treatment.Item Navigating liver cancer: precision targeting for enhanced treatment outcomes(Springer, 2025-01) Jain, AnkitCancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.