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用于在模拟活性氧环境中递送抗氧化剂的含醋酸视黄酯聚己内酯电纺纤维的制备

Fabrication of polycaprolactone electrospun fibres with retinyl acetate for antioxidant delivery in a ROS-mimicking environment.

作者信息

Westwood Lorna, Emmerson Elaine, Callanan Anthony

机构信息

School of Engineering, Institute for Bioengineering, University of Edinburgh, Edinburgh, United Kingdom.

The Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.

出版信息

Front Bioeng Biotechnol. 2023 Aug 15;11:1233801. doi: 10.3389/fbioe.2023.1233801. eCollection 2023.

Abstract

Increased cancer rates denote that one in two people will be diagnosed with cancer in their lifetime. Over 60% of cancer patients receive radiotherapy, either as a stand-alone treatment or in combination with other treatments such as chemotherapy and surgery. Whilst radiotherapy is effective in destroying cancer cells, it also causes subsequent damage to healthy cells and surrounding tissue due to alterations in the tumor microenvironment and an increase in reactive oxygen species (ROS). This can cause extensive damage that impairs tissue function, and the likelihood of tissue regeneration and restoration of function is significantly reduced as new healthy cells cannot survive in the damaged environment. In the treatment of head and neck cancers, radiotherapy can cause salivary gland dysfunction. This significantly impairs the patient's quality of life and there is currently no cure, only palliative treatment options. Tissue engineering approaches are used to mimic the microenvironment of the tissue and can mediate the damaged microenvironment via bioactive compounds, to support the delivery, survival, and proliferation of new, healthy cells into the damaged environment. In this study, retinyl acetate, a derivative of vitamin A, was successfully incorporated into electrospun polycaprolactone fibres. SEM images and characterization analyses showed that all scaffolds produced had similar characteristics, including fiber morphology and scaffold wettability. The vitamin scaffolds were shown to exert an antioxidant effect through scavenging activity of both DPPH and hydroxyl radicals . Critically, the antioxidant scaffolds supported the growth of human submandibular gland cells and significantly upregulated the expression of , an antioxidant enzyme, when cultured under both normal conditions and under a simulated oxidative stress environment. These results suggest that incorporation of retinyl acetate into electrospun fibres has may mediate the damaged microenvironment post cancer radiation therapy.

摘要

癌症发病率的上升意味着每两个人中就有一人在其一生中会被诊断出患有癌症。超过60%的癌症患者接受放射治疗,无论是作为单独的治疗方法,还是与化疗和手术等其他治疗方法联合使用。虽然放射治疗在破坏癌细胞方面是有效的,但由于肿瘤微环境的改变和活性氧(ROS)的增加,它也会对健康细胞和周围组织造成后续损伤。这可能会导致广泛的损伤,损害组织功能,并且由于新的健康细胞无法在受损环境中存活,组织再生和功能恢复的可能性会显著降低。在头颈部癌症的治疗中,放射治疗会导致唾液腺功能障碍。这会严重损害患者的生活质量,目前尚无治愈方法,只有姑息治疗选择。组织工程方法用于模拟组织的微环境,并可以通过生物活性化合物介导受损的微环境,以支持新的健康细胞向受损环境的递送、存活和增殖。在本研究中,维生素A的衍生物醋酸视黄酯成功地掺入到电纺聚己内酯纤维中。扫描电子显微镜(SEM)图像和表征分析表明,所有制备的支架具有相似的特性,包括纤维形态和支架润湿性。维生素支架通过对DPPH和羟基自由基的清除活性表现出抗氧化作用。至关重要的是,当在正常条件和模拟氧化应激环境下培养时,抗氧化支架支持人下颌下腺细胞的生长,并显著上调一种抗氧化酶的表达。这些结果表明,将醋酸视黄酯掺入电纺纤维中可能介导癌症放射治疗后的受损微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/10463743/98fafbf3e25d/fbioe-11-1233801-g001.jpg

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