Archives of biochemistry and biophysics最新文献

{"title":"In silico based re-engineering of a computationally designed biosensor with altered signalling mode and improved dynamic range","authors":"Dustin D. Smith ,&nbsp;D. Wade Abbott ,&nbsp;Hans-Joachim Wieden","doi":"10.1016/j.abb.2024.110275","DOIUrl":"10.1016/j.abb.2024.110275","url":null,"abstract":"<div><div>A current challenge in the rational design of biomolecular sensors is the ability to custom design binding affinities and detection mode <em>in silico</em>. To this end, we re-engineered a previously reported computationally-designed fluorescent maltooligosaccharide (MOS)-detecting biosensor to both alter its ligand-binding affinity and to analyse the underlying sensing mechanism. The dynamic range of the biosensor was expanded through the computer aided introduction of a series of amino acid substitutions in the starting protein scaffold (MalX from <em>Streptococcus pneumoniae</em>), which generated a biosensor set with binding affinities spanning over five orders of magnitude. The impact of the introduced substitutions on the underlying mode of signal generation was assessed <em>in silico</em> using our previously reported Computational Identification of Non-disruptive Conjugation sites (CINC) pipeline. CINC utilizes molecular dynamics simulations and an in-house developed algorithm to examine and exploit the structural dynamics of a protein at amino acid-level resolution. Using CINC, we demonstrate that re-engineering of the MOS-detecting biosensor set resulted in sensors with two distinct output modes which differed based on local conformational changes at the fluorescently modified reporter position. These output modes were classified as “ligand-sensing”-type biosensors (readout based on the tool sensing a unique conformation in the ligand-bound state), and “<em>apo</em>-sensing”-type biosensors (readout based on the tool sensing a unique conformation in the <em>apo</em> state). Together, these results demonstrate that structural dynamics at the individual amino acid residue level can be used as an engineer-able feature to rationally alter the fluorescence reporting properties of a biosensing device. Moving forward, the CINC workflow can also be adapted for the rational design of protein dynamic properties maximizing its utility as an <em>in silico</em> design platform for custom biomolecular tools.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110275"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effect of cerium nanoparticles on the viability, redox-status and Ca2+-signaling system of cancer cells of various origins","authors":"Elena G. Varlamova ,&nbsp;Sergey V. Gudkov ,&nbsp;Egor A. Turovsky","doi":"10.1016/j.abb.2024.110261","DOIUrl":"10.1016/j.abb.2024.110261","url":null,"abstract":"<div><div>The present study aims to understand the molecular mechanism underlying the therapeutic effect of cerium nanoparticles (CeNPs) in oncology. Cancer cells were treated with different concentrations of pure nanocerium of different sizes synthesized by laser ablation. Due to the not insignificant influence of surface defects and oxygen species on the ROS-modulating properties of cerium nanoparticles, the nanoparticles were not coated with surfactants or organic molecules during synthesis, which could potentially inhibit a number of pro-oxidative effects. Reactive oxygen species (ROS) production, expression of genes encoding redox-status proteins, selenoproteins and proteins regulating cell death and endoplasmic reticulum stress (ER-stress) were investigated as indicators of the molecular mechanism of cancer cell death. Studies were conducted on the effects of cerium nanoparticles on the Ca²⁺ signaling system of cancer cells of different origins. Mouse fibroblasts (L-929 cell line) were used as non-cancerous (“normal”) cells for which a whole series of experiments were performed, and a comparative analysis of the effects of nanoceria. It was found that 75 nm-sized cerium nanoparticles did not affect the redox-status and ROS production of cancer cells. In fibroblast cells, however, this nanoparticle diameter led to a deterioration of the cellular redox status and ROS production in a wide range of nanoparticle concentrations. Larger nanoparticles (100 nm-sized and 160 nm-sized), on the other hand, showed a different effect on cancer cells of different origins. In mouse fibroblast L-929 cells, however, 100 nm-sized or 160 nm-sized CeNPs acted in a high concentration range to disrupt mitochondrial membrane potential and activate early apoptosis. High concentrations of CeNPs were required to increase ROS production, reduce redox-status and induce apoptosis in human A-172 glioblastoma cells compared to the hepatocellular carcinoma cell line HepG2 and the breast cancer cell line MCF-7. In the A-172 glioblastoma cells, ER-stress was also not activated and their Ca²⁺ signaling system was activated by a significantly higher concentration of CeNPs, which could also contribute to the formation of tolerance of this cancer cell line to nanoceria. The Ca²⁺ signaling system of mouse fibroblasts was found to be highly sensitive to activation by nanoceria and the cells produced Ca2+ signals with higher amplitude compared to A-172 and MCF-7 cells.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110261"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MD simulations for rational design of high-affinity HDAC4 inhibitors – Analysis of non-bonding interaction energies for building new compounds","authors":"Varun Dewaker ,&nbsp;Pratik Narain Srivastava ,&nbsp;Utsab Debnath ,&nbsp;Ajay Kumar Srivastava ,&nbsp;Yenamandra S. Prabhakar","doi":"10.1016/j.abb.2024.110262","DOIUrl":"10.1016/j.abb.2024.110262","url":null,"abstract":"<div><div>This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (<strong>HA3</strong>, <strong>9F4</strong>, <strong>EBE</strong>, and <strong>TFG</strong>) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (<strong>HA3</strong>, <strong>9F4</strong>, <strong>EBE</strong>) or diol (<strong>TFG</strong>) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation. We identified <strong>HA3</strong> as a weaker inhibitor because of the unfavorable NBE contributions from its carbonyl fragment (<strong>FR3</strong>) and hydroxamic fragment (<strong>FR1</strong>). To enhance NBE efficacy, we designed novel <strong>HA3</strong> analogs (<strong>H01</strong>–<strong>H16</strong>) by introducing diverse fragments (–CF3, 2-hydroxyacetic acid, -NH-CH2-, 5-fluoro-2-phenyl pyrimidine, and chloroquinoline moieties). MD simulations revealed promising analogs (<strong>H02</strong>, <strong>H07</strong>, <strong>H08</strong>, <strong>H15</strong>) with strong NBEs and stable ligand-zinc retention (2.07–2.33 Å). These analogs exhibited strong relative binding free energies within their catalytic sites, highlighting their potential as novel HDAC4 inhibitors. The current study provides medicinal chemists with insights into non-covalent interactions, identifies key fragments for optimization, and offers a rational design strategy for developing more effective HDAC4 inhibitors.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110262"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential structural characteristics, physicochemical properties, and calcium-binding capabilities of annexin A2 wild-type versus E53A, E96A, D162A, E247A and D322A mutants","authors":"Sunisa Yoodee,&nbsp;Sirikanya Plumworasawat,&nbsp;Thanyalak Malaitad,&nbsp;Paleerath Peerapen,&nbsp;Visith Thongboonkerd","doi":"10.1016/j.abb.2024.110267","DOIUrl":"10.1016/j.abb.2024.110267","url":null,"abstract":"<div><div>Annexin A2 (ANXA2) is a Ca²⁺-dependent multifunctional protein containing five Ca²⁺-binding domains, but their functional significance and difference remain unclear. Herein, glutamic acid (E) or aspartic acid (D) in five Ca²⁺-binding domains of canine ANXA2 (98.82 % and 96.76–99.41 % identical to ANXA2 from human and other mammals, respectively) was substituted by alanine (A) using site-directed mutagenesis. Recombinant ANXA2 wild-type (WT) and E53A, E96A, D162A, E247A and D322A mutants were constructed and expressed using a bacterial expression system followed by high-affinity purification using nickel-nitrilotriacetic acid (Ni-NTA) matrix. Efficacies of their expression and purification were confirmed by SDS-PAGE and Western blotting. Their amino acid sequences were verified by nanoLC-ESI-Qq-TOF tandem mass spectrometry. ATR-FTIR spectroscopy revealed that their secondary structure significantly differed (α-helix decreased but random coil increased in all mutants). Analyses of physicochemical properties revealed that molecular weight slightly decreased, whereas isoelectric point, aliphatic index, grand average of hydropathicity, electrostatic potential and molecular hydrophobicity potential slightly increased in all the mutants compared with WT. Interestingly, Ca²⁺-binding capability of these mutants (particularly E96A and D322A) significantly decreased from that of WT. In summary, secondary structure, physicochemical properties, and Ca²⁺-binding capability of E53A, E96A, D162A, E247A and D322A mutants of ANXA2 significantly differed from its WT, consistent with the loss of negatively charged E/D. In particular, E96A and D322A exhibited the lowest Ca²⁺-binding capability. These data and recombinant proteins would be useful for further investigations of the Ca²⁺-dependent functions of individual Ca²⁺-binding domains in ANXA2.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110267"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of ABC transporter Cdr1 inhibitors of Candida glabrata","authors":"Mohd Waseem ,&nbsp;Shubhashis Das ,&nbsp;Debarati Mondal ,&nbsp;Anuj Kumari ,&nbsp;Ritu Kulshreshtha ,&nbsp;Jitendra K. Thakur ,&nbsp;Naidu Subbarao","doi":"10.1016/j.abb.2024.110270","DOIUrl":"10.1016/j.abb.2024.110270","url":null,"abstract":"<div><div><em>Candida glabrata is</em> one of the most common causes of invasive candidiasis. Rising treatment failures from resistance to current antifungal drugs highlight the need for new antifungals. Overexpression of efflux pump transporter genes is significantly associated with the development of multidrug resistance. In this study, we have identified novel and potential inhibitors of ABC transporter Cdr1 of <em>Candida glabrata</em> (<em>Cg</em>Cdr1) by employing high throughput virtual screening of large chemical datasets from five different chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, and ChEMBL bioassay). As a result many molecules were predicted to have higher binding affinity toward the <em>Cg</em>Cdr1, in which a naturally occurring compound, pentagalloyl glucose, was identified to significantly reduce the growth of <em>Candida glabrata</em> with an IC₅₀ value of 16.97 ± 2.1 μM. Molecular dynamics studies showed stable binding of pentagalloyl glucose with <em>Cg</em>Cdr1 protein. In summary, our research identifies pentagalloyl glucose as a novel antifungal compound that has the potential to be used for inhibiting the growth of <em>Candida glabrata</em>.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110270"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis","authors":"Chenyan Zhang ,&nbsp;Yile Tian ,&nbsp;Xinli Liu ,&nbsp;Xuezhou Yang ,&nbsp;Shanfeng Jiang ,&nbsp;Ge Zhang ,&nbsp;Changqing Yang ,&nbsp;Wenjing Liu ,&nbsp;Weihong Guo ,&nbsp;Wenzhe Zhao ,&nbsp;Dachuan Yin","doi":"10.1016/j.abb.2024.110273","DOIUrl":"10.1016/j.abb.2024.110273","url":null,"abstract":"<div><div>Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both <em>in vitro</em> and <em>in vivo</em>, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model. Enforced miR-495 expression by its mimic could enormously facilitate the differentiation and regeneration of both mouse myoblast C2C12 cells and muscle satellite cells<em>.</em> Furthermore, MyoD was proved as the directly interacted gene of miR-495, and their interaction was crucial for myotube formation. Enforced miR-495 expression could intensively strengthen the muscle mass, <em>in situ</em> muscular electrophysiological indexes, including peak tetanic tension (Po) and peak twitch tension (Pt), and the cross-sectional areas (CSA) of muscle fibers via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 signaling pathway, indicating that miR-495 can be proposed as an effective target for muscle atrophy treatment induced by in the mechanical unloading, random rotating and aging.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110273"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation","authors":"Ting Zhou ,&nbsp;Xiaorong Li ,&nbsp;Fangfang Zhao ,&nbsp;Jing Zhou ,&nbsp;Binghui Sun","doi":"10.1016/j.abb.2024.110287","DOIUrl":"10.1016/j.abb.2024.110287","url":null,"abstract":"<div><h3>Background</h3><div>Lactamase β (LACTB) inhibits the metastasis and progression of multiple malignant tumors. However, little is known about its role in endometrial cancer (EC). Our study aimed to investigate the function and potential molecular mechanism of LACTB in modulating EC progression.</div></div><div><h3>Methods</h3><div>LACTB expression was measured via immunohistochemistry staining, Western blot and qRT-PCR. The role of LACTB in EC was investigated both in vivo and in vitro by employing xenograft mice models and using colony formation, EdU, and Transwell assays, along with flow cytometric analysis. In addition, to assess LACTB function on lipid metabolism, lipid droplets in EC cells were labeled with Nile red. Western blot, immunofluorescence staining, co-immunoprecipitation, ubiquitination assay, and cycloheximide chase assay and rescue experiments were performed to confirm the interaction between LACTB, p53, and MDM2 in EC.</div></div><div><h3>Results</h3><div>LACTB expression was downregulated in EC. LACTB inhibited the malignant phenotypes and reprogramed lipid metabolism in EC cells. Moreover, LACTB significantly upregulated p53 by attenuating the MDM2-mediated ubiquitination and degradation of p53. Besides, LACTB silencing facilitated the malignant phenotypes and reprogramed lipid metabolism in EC cells; this was reversed with p53 overexpression. LACTB knockdown facilitated EC progression via downregulating p53 in vivo.</div></div><div><h3>Conclusion</h3><div>LACTB repressed EC cell proliferation and metastasis, and reprogramed lipid metabolism via attenuating the MDM2-mediated ubiquitination and degradation of p53.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110287"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities","authors":"Manasi S. Pote,&nbsp;Rajesh N. Gacche","doi":"10.1016/j.abb.2024.110277","DOIUrl":"10.1016/j.abb.2024.110277","url":null,"abstract":"<div><div>Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them. Exosome-mediated cell-to-cell communication has reportedly been shown to affect multiple cancer hallmarks, such as immune response modulation, pre-metastatic niche formation, angiogenesis, stromal cell reprogramming, extracellular matrix architecture remodeling, or even drug resistance, and eventually the development and metastasis of cancer cells. Exosomes can be used as therapeutic targets and possible diagnostic biomarkers by selectively loading oncogenic molecules into them. We highlight the important roles that exosomes play in cancer development in this review, which may lead to the development of fresh approaches for future clinical uses.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110277"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of anti-tumor small molecule lead compounds targeting the SH3 domain of c-Src protein through virtual screening and biological evaluation","authors":"Haifang Hao ,&nbsp;Yuan Bian ,&nbsp;Na Yang ,&nbsp;Xingzhao Ji ,&nbsp;Jie Bao ,&nbsp;Kongkai Zhu","doi":"10.1016/j.abb.2024.110286","DOIUrl":"10.1016/j.abb.2024.110286","url":null,"abstract":"<div><div>c-Src, also known as cellular Src, is a non-receptor tyrosine kinase that plays a crucial role in various cellular processes, including cell proliferation, adhesion, and migration. Its dysregulation has been implicated in the development and progression of several diseases, particularly cancer. Current therapeutic agents targeting c-Src are primarily small molecules binding to its kinase domain. However, drug resistance often reduces the effectiveness of these drugs. The SH3 domain of c-Src is a highly conserved functional region with a low propensity for developing drug resistance, whereas there are no existing anti-cancer drugs specifically binding to this domain. In this study, structure-based virtual screening and thermal shift experimental verification identified three molecules that showed potent binding affinity with SH3 domain of c-Src. Subsequent kinase activity assay validated the inhibitory activity of these compounds against c-Src, with IC₅₀ values ranging from 60.42 to 122.2 nM. Next, cell-level assays and preliminary study were conducted to further evaluate the efficacy of the identified active compounds. In conclusion, the present work has provided new chemical templates as lead structures for the future development of new antitumor therapeutics targeting the c-Src SH3 domain to overcome drug resistance.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110286"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosensitization impact assessment of silica-layered iron oxide nanocomposites with various shell thickness","authors":"Mohamed M. Fathy,&nbsp;Omnia A. Saad,&nbsp;Heba M. Fahmy","doi":"10.1016/j.abb.2024.110257","DOIUrl":"10.1016/j.abb.2024.110257","url":null,"abstract":"<div><div>Silica shell is considered to be a promising design that enhances nanocomposite stability, cellular internalization, and consequentially therapeutic impacts by overcoming their aggregation under physiological conditions. This study addressed synthesizing silica-layered iron oxide-based nanoparticles (SCINPs) with different shell thicknesses (1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs). Also, the impact of shell thickness on the nanoparticle's cellular internalization and the radio-sensitizing effect of prepared nano-formulations were assessed. The physical properties of the synthesized nanoparticles were examined using transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), and X-ray diffraction (XRD). Cytotoxicity assay, oxidative stress parameters, and comet assay were used to investigate the radio-sensitizing effect of various nanoformulations. Results revealed that the mean diameter of prepared oxide-based nanoparticles (INPs) was about 12.63 ± 1.36 nm, and the shell thickness for 1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs was 22.58 ± 3.51, 26.13 ± 1.40, 46.95 ± 3.10 and 60.30 ± 4.30 nm, respectively. Interestingly, we found that in cells treated with 40 μg/ml of INPs, their viability decreased to 44.6 %. Meanwhile, the viability was 41.69 % and 39.4 % for cells treated with 1-SCINPs and 2-SCINPs, respectively. This means that a thicker silica shell led to a decreased impact on radiosensitization. This was attributed to the influence of surface properties and size of SCINPs on their cellular uptake and the secondary electrons' entrapment within thicker shells upon radiation exposure. Cell viability test, comet assay and oxidative stress parameters show that 2-SCINPs formulations had the most potent radiosensitizing effect (with the highest dose enhancement factor equal to 2.1) when combined with radio-treatment. The results suggest that optimizing the silica shell thickness is critical for maximizing the therapeutic efficacy of SCINPs, with 2-SCINPs showing the highest radiosensitization effect.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110257"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}