Abstract
PurposeTherapeutic thorax irradiation as an intervention in lung cancer has its limitations due to toxic effects leading to pneumonitis and/or pulmonary fibrosis. It has already been confirmed that hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, is involved in inflammation disorders and wound healing in lung tissue. We examined the effects after gamma irradiation of hyaluronic acid nanoparticles (HANPs) applied into lung prior to that irradiation in a dose causing radiation-induced pulmonary injuries (RIPI).Materials and MethodsBiocompatible HANPs were first used for viability assay conducted on the J774.2 cell line. For in vivo experiments, HANPs were administered intratracheally to C57Bl/6 mice 30 min before thoracic irradiation by 17 Gy. Molecular, cellular, and histopathological parameters were measured in lung and peripheral blood at days 113, 155, and 190, corresponding to periods of significant morphological and/or biochemical alterations of RIPI.ResultsModification of linear hyaluronic acid molecule into nanoparticles structure significantly affected the physiological properties and caused long-term stability against ionizing radiation. The HANPs treatments had significant effects on the expression of the cytokines and particularly on the pro-fibrotic signaling pathway in the lung tissue. The radiation fibrosis phase was altered significantly in comparison with a solely irradiated group.ConclusionsThe present study provides evidence that application of HANPs caused significant changes in molecular and cellular patterns associated with RIPI. These findings suggest that HANPs could diminish detrimental radiation-induced processes in lung tissue, thereby potentially decreasing the extracellular matrix degradation leading to lung fibrosis.
Highlights
Despite the many great advances in the field of radiotherapy, radiation toxicity remains a serious complication in patients receiving such therapy
Two types of HA assembled into NPs (HANPs) were prepared by covalent cross-linking of hyaluronic acid (HA) chains while using acid dihydrazide (AAD) as a cross-linking agent
HANPs were first prepared by a simple crosslinking method. These HANPs were used as an initial solution for double cross-linking procedure, the aim being to reduce their size
Summary
Despite the many great advances in the field of radiotherapy, radiation toxicity remains a serious complication in patients receiving such therapy. Initial damage induces expression of multiple cytokines and growth factors in specific cell types within lung tissue This is followed by activation of various signaling pathways and results in the development of subsequent pathophysiological processes. The endothelial-to-mesenchymal transition of vascular endothelial cell has been identified as contributing factor to development of RF (Choi et al, 2015) From another point of view, RF may be perceived as insufficient wound healing characterized by extensive deposition of connective tissue that is followed by destruction of the lung parenchyma to form fibrotic lesions (Straub et al, 2015). Both concepts emphasize the role of transforming growth factor b (TGF-b) and its signaling, but accumulating evidence points to the role of ECM components in the fibrotic process (Wegrowski et al, 1992; Bensadoun et al, 1996; Albeiroti et al, 2015; Collum et al, 2019)
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