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Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model.

ABSTRACT: Pancreatic cancer stands among the deadliest forms of cancer, and the existing treatments fall short of providing adequate efficacy. Novel and more effective treatment approaches are urgently required to address this critical medical challenge. In this study, we aimed to evaluate the anti-cancer efficacy of gold nanoparticles (GNPs) in combination with radiotherapy (RT). A 3D pancreatic cancer co-culture spheroid model of MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts (CAF-98) was used. The spheroids were treated with GNPs (7.5 μg/mL) and 2 Gy of RT. The spheroids' cell viability was assessed through the CellTiter-Glo 3D assay, and an immunofluorescence assay was used to assess the DNA DSBs via the expression of the DNA damage marker 53BP1. Co-culture samples showed a 10.8% (p < 0.05) increase in proliferation and a 13.0% (p < 0.05) decrease in DNA DSB when compared to monoculture samples, However, they displayed a 175% (p < 0.001) increase in GNPs uptake when compared to monoculture spheroids. Using GNPs/RT, we were able to show a significant reduction of 6.2% (p < 0.05) in spheroid size and an increase of 14.3% (p < 0.05) in DNA DSB damage in co-culture samples. The combination of GNPs with RT demonstrated remarkable radiosensitization effects, representing a promising approach to enhance cancer treatment efficacy. These effects were particularly noteworthy in the more treatment-resistant co-culture spheroid model.

SUBMITTER: Alhussan A

PROVIDER: S-EPMC10419973 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model.

Alhussan Abdulaziz A Jackson Nolan N Calisin Reinali R Morgan Jessica J Beckham Wayne W Chithrani Devika B DB

International journal of molecular sciences 20230807 15

Pancreatic cancer stands among the deadliest forms of cancer, and the existing treatments fall short of providing adequate efficacy. Novel and more effective treatment approaches are urgently required to address this critical medical challenge. In this study, we aimed to evaluate the anti-cancer efficacy of gold nanoparticles (GNPs) in combination with radiotherapy (RT). A 3D pancreatic cancer co-culture spheroid model of MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts ...[more]

PMID: 37569898

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Project description:Approaches for the creation of soft materials, particularly hydrogels, with hierarchical structure are of interest in a variety of applications owing to their unique properties. In the context of tissue mimics, hydrogels with multiscale structures more accurately capture the complexities of tissues within the body (e.g., fibrous collagen-rich microenvironments). However, cytocompatible fabrication of such materials with hierarchical structures and independent control of mechanical and biochemical properties remains challenging and is needed for probing and directing cell-microenvironment interactions for three-dimensional (3D) cell encapsulation and culture applications. To address this, we have designed innovative multifunctional assembling peptides: these unique peptides contain a core block that mimics the structure of collagen for achieving relevant melting temperatures; 'sticky' ends to promote assembly of long fibrils; and a biocompatible reactive handle that is orthogonal to assembly to allow the formation of desired multiscale structures and their subsequent rapid, light-triggered integration within covalently crosslinked synthetic hydrogels. Nano- to micro-fibrils were observed to form in physiologically-relevant aqueous solutions, where both underlying peptide chemical structure and assembly conditions were observed to impact the resulting fibril sizes. These assembled structures were 'locked' into place and integrated as linkers within cell-degradable, bioactive hydrogels formed with photoinitiated thiol-ene 'click' chemistry. Hydrogel compositions were identified for achieving robust mechanical properties like those of soft tissues while also retaining higher ordered structures after photopolymerization. The utility of these innovative materials for 3D cell culture was demonstrated with human mesenchymal stem cells, where cell morphologies reminiscent of responses to assembled native collagen were observed now with a fully synthetic material. Using a bottom-up approach, a new materials platform has been established that combines the advantageous properties of covalent and assembling chemistries for the creation of synthetic hydrogels with controllable nanostructure, mechanical properties, and biochemical content.

Dataset Information

Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model.

Publications

Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model.

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