Dataset Information

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

ABSTRACT: Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

SUBMITTER: Kouri MA

PROVIDER: S-EPMC10742116 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Kouri Maria Anthi MA Spyratou Ellas E Kalkou Maria-Eleni ME Patatoukas Georgios G Angelopoulou Evangelia E Tremi Ioanna I Havaki Sophia S Gorgoulis Vassilis G VG Kouloulias Vassilis V Platoni Kalliopi K Efstathopoulos Efstathios P EP

Biomolecules 20231129 12

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of Au ...[more]

PMID: 38136591

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Project description:Background:Gold nanoparticles (GNPs) are among the most promising radiosensitive materials in radiotherapy. Studying the effective sensitizing factors such as nanoparticle size, concentration, surface features, radiation energy and cell type can help to optimize the effect and possible clinical application of GNPs in radiation therapy. In this study, the radiation sensitive polymer gel was used to investigate the dosimetric effect of GNP size in megavoltage (MV) photon beam radiotherapy. Material and Methods:GNPs with the size of 30nm, 50nm and 100nm in diameter were used. Transmission electron microscope (TEM) and dynamic light scattering (DLS) were applied to analyze the size of nanoparticles. The MAGICA polymer gel was synthesized and impregnated with different sizes of GNPs. The samples were irradiated with 6MV photon beam and 24 hours after irradiation, they were read using a Magnetic Resonance Imaging (MRI) scanner. Macroscopic Dose Enhancement Factor (DEF) was measured to compare the effect of GNP size. The MAGICA response of the 6MV x-ray beam was verified comparing Percentage Depth Dose (PDD) curve extracted from polymer gel dosimetry and Treatment Planning System (TPS). Results:MAGICA polymer gel dose response curve was linear in the range of 0 to 10 Gy. DEFs by adding 30nm, 50nm and 100nm GNPs were 1.1, 1.17 and 1.12, respectively. PDD curves of polymer gel dosimeter and treatment planning system were in good agreement. Conclusion:The results indicated a substantial increase in DEF uses a MV photon beam in combination with GNPs of different sizes and it was inconsistent with previous radiobiological studies. The maximum DEF was achieved for 50nm GNPs in comparison with 30nm and 100nm leading to the assumption of self-absorption effect by larger diameters. According to the outcomes of this work, MAGICA polymer gel can be recommended as a reliable dosimeter to investigate the dosimetric effect of GNP size and also a useful method to validate the current radiobiological and simulation studies.

Project description:Immune-mediated hypersensitivities such as autoimmunity, allergy, and allogeneic graft rejection are treated with therapeutics that suppress the immune system, and the lack of specificity is associated with significant side effects. The delivery of disease-relevant antigens (Ags) by carrier systems such as poly(lactide-co-glycolide) nanoparticles (PLG-Ag) and carbodiimide (ECDI)-fixed splenocytes (SP-Ag) has demonstrated Ag-specific tolerance induction in model systems of these diseases. Despite therapeutic outcomes by both platforms, tolerance is conferred with different efficacy. This investigation evaluated Ag loading and total particle dose of PLG-Ag on Ag presentation in a coculture system of dendritic cells (DCs) and Ag-restricted T cells, with SP-Ag employed as a control. CD25 expression was observed in nearly all T cells even at low concentrations of PLG-Ag, indicating efficient presentation of Ag by dendritic cells. However, the secretion of IL-2, Th1, and Th2 cytokines (IFNγ and IL-4, respectively) varied depending on PLG-Ag concentration and Ag loading. Concentration escalation of soluble Ag resulted in an increase in IL-2 and IFNγ and a decrease in IL-4. Treatment with PLG-Ag followed a similar trend but with lower levels of IL-2 and IFNγ secreted. Transcriptional Activity CEll ARrays (TRACER) were employed to measure the real-time transcription factor (TF) activity in Ag-presenting DCs. The kinetics and magnitude of TF activity was dependent on the Ag delivery method, concentration, and Ag loading. Ag positively regulated IRF1 activity and, as carriers, NPs and ECDI-treated SP negatively regulated this signaling. The effect of Ag loading and dose on tolerance induction were corroborated in vivo using the delayed-type hypersensitivity (DTH) and experimental autoimmune encephalomyelitis (EAE) mouse models where a threshold of 8 μg/mg Ag loading and 0.5 mg PLG-Ag dose were required for tolerance. Together, the effect of Ag loading and dosing on in vitro and in vivo immune regulation provide useful insights for translating Ag-carrier systems for the clinical treatment of immune disorders.

Project description:Serum-driven responses, many of which are related to wound healing, are potentially deregulated in cancer development and associated genomic alterations might have prognostic value. The current study assessed fetal bovine serum-induced transcriptomic changes for clinical relevance in head and neck squamous cell carcinoma (HNSCC) using oral keratinocyte models otherwise routinely cultured without serum, including normal keratinocytes (NOK) and the transformed keratinocyte lines SVpgC2a, SqCC/Y1 and LK0412. Bioinformatics-driven analysis of gene expression implicated primarily serum-induced terminal differentiation in NOK including alterations in 99 genes, 13 gene ontology-categories and 6 molecular networks and involvement of 7 key regulator genes. Compared to NOK, the transformed lines expressed around 3-fold lower numbers of differently expressed transcripts, unique sets of gene ontologies, molecular networks and key regulator genes for each line, and consistent absence of terminal differentiation markers. Assessment of the complete in vitro/serum exposure-derived set of differentially expressed genes (totally 180 genes) relative a clinical, information-rich HNSCC data set identified 17 survival-associated genes of which only 12 had previous association to HNSCC. Multi-step validation of the survival-associated genes relative to several independent tumor data sets, including in the Human Gene Expression Map and Human Protein Atlas databases, confirmed novel association to HNSCC for genes COTL1 and INSIG1 and novel poor outcome prediction for the genes CUL4B and PDGFRL. The definition of normal and aberrant serum responses in keratinocyte models therefore coupled new genes to HNSCC including with relevance to prognosis. Analysis of gene expression changes in serum-exposed normal and transformed cells relative the respective un-exposed states. Significantly differentially expressed genes were next assessed by bioinformatics processing using Gene Ontology categories and network analyses. Findings were also validated relative independent HNSCC data sets as well as transcriptomics and proteomics databases.

Dataset Information

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Publications

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

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