Enhancing the Efficacy of Radiation Therapy by Photochemical Internalization of Fibrin-Hydrogel-Delivered Bleomycin

Abstract

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.