The rapid proliferation of tumor cells and tortuous vasculature in solid tumors often bring about a hypoxic tumor microenvironment, which renders tumor cells more resistant to many cancer treatments, including radiotherapy. In this study, an injectable and thermosensitive composite hydrogel composed of perfluorooctanoic acid (PFOA) modified monomethoxy poly(ethylene glycol)–poly(D,L-lactide-co-glycolide) (mPEG–PLGA–PFOA) and perfluorooctyl bromide (PFOB) that presented a thermoreversible sol–gel transition upon heating was developed to deliver exogenous oxygen for the relief of tumor hypoxia and enhancement of radiotherapy. The fluorinated modification of copolymers significantly increased the stability of PFOB in the mPEG–PLGA–PFOA aqueous solution owing to the fluorophilic interaction between PFOB and PFOA-modified copolymers. The introduction of PFOB not only efficiently heightened the oxygen loading capacity of the composite hydrogel, but also endowed it with excellent X-ray opacity, allowing the visual observation of the hydrogel via micro-CT imaging. After peritumoral injection of the oxygen-enriched composite hydrogel, the continuous supply of oxygen effectively relieved tumor hypoxia and down-regulated the expression of hypoxia-inducible factor-1α. Profiting from this, the hyposensitivity of tumor cells to radiation was successfully reversed, and the tumor growth in mice was significantly suppressed and the survival of mice was prolonged when combined with multiple X-ray exposure. As a result, the oxygen-enriched composite hydrogel shows a great potential for radiosensitization to improve the radiotherapeutic efficacy.

中文翻译：

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用于缓解缺氧肿瘤微环境和增强放射治疗的富氧热敏水凝胶

实体瘤中肿瘤细胞的快速增殖和曲折的脉管系统往往会导致低氧的肿瘤微环境，这使得肿瘤细胞对包括放射治疗在内的许多癌症治疗更具抵抗力。在本研究中，全氟辛酸（PFOA）改性单甲氧基聚（乙二醇）-聚（D，L-丙交酯-co ）组成的可注射热敏复合水凝胶-乙交酯）（mPEG-PLGA-PFOA）和全氟辛基溴（PFOB）在加热时呈现出热可逆的溶胶-凝胶转变，被开发用于输送外源性氧气以缓解肿瘤缺氧和增强放射治疗。由于 PFOB 和 PFOA 改性共聚物之间的亲氟相互作用，共聚物的氟化改性显着提高了 PFOB 在 mPEG-PLGA-PFOA 水溶液中的稳定性。PFOB的引入不仅有效地提高了复合水凝胶的载氧能力，而且赋予了它优异的X射线不透光性，可以通过目视观察水凝胶。显微CT成像。瘤周注射富氧复合水凝胶后，持续供氧有效缓解了肿瘤缺氧，下调了缺氧诱导因子-1α的表达。得益于此，肿瘤细胞对辐射的低敏感性被成功逆转，小鼠体内的肿瘤生长得到显着抑制，并在与多次X射线照射相结合的情况下延长了小鼠的生存期。因此，富氧复合水凝胶显示出巨大的放射增敏潜力，可提高放射治疗效果。