Background/Objectives: Although the use of radiation-sensitizing agents has been shown to enhance the effect of radiation on tumor cells, the blood–brain barrier (BBB) impedes these agents from reaching brain tumor sites when provided systemically. Localized methods of sensitizer delivery, utilizing hydrogels, have the potential to bypass the blood–brain barrier. This study examined the ability of photochemical internalization (PCI) of hydrogel-released bleomycin to enhance the growth-inhibiting effects of radiation on multi-cell glioma spheroids in vitro. Methods: Loaded fibrin hydrogel layers were created by combining thrombin, fibrinogen, and bleomycin (BLM). Supernatants from these layers were collected, combined with photosensitizer, and added to F98 glioma spheroid cultures. Following light (PCI) and radiation treatment, at increasing dosages, spheroid growth was monitored for 14 days. Results: PCI of released BLM significantly reduced the radiation dose required to achieve equivalent efficacy compared to radiation or BLM + RT alone. Both immediate and delayed RT delivery post-BLM-PCI resulted in similar degrees of growth inhibition. Conclusions: Non-degraded BLM was released from the fibrin hydrogel. PCI of BLM synergistically increased the growth-inhibiting effects of radiation treatment compared to radiation and BLM, as well as radiation acting as a single treatment.
背景/目的：尽管放射增敏剂的使用已被证实能增强放射线对肿瘤细胞的作用，但当通过全身给药时，血脑屏障（BBB）会阻碍这些药物到达脑肿瘤部位。利用水凝胶进行局部增敏剂递送的方法，有可能绕过血脑屏障。本研究探讨了水凝胶释放的博来霉素通过光化学内化作用（PCI）在体外增强放射线对多细胞胶质瘤球体生长抑制效果的能力。方法：通过混合凝血酶、纤维蛋白原和博来霉素（BLM）制备负载纤维蛋白水凝胶层。收集这些水凝胶层的上清液，与光敏剂混合后加入F98胶质瘤球体培养物中。在光（PCI）和不同剂量放射线处理后，监测球体生长14天。结果：与单独使用放射线或BLM+放射线治疗相比，释放的BLM的PCI显著降低了达到同等疗效所需的放射剂量。在BLM-PCI后立即或延迟给予放射线治疗，均能产生相似程度的生长抑制效果。结论：未降解的BLM可从纤维蛋白水凝胶中释放。与单独使用放射线或BLM联合放射线治疗相比，BLM的PCI能协同增强放射治疗的生长抑制效果，其效果优于放射线单一治疗。
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