Abstract
Higher doses of radiotherapy (RT) are associated with resistance induction, therefore highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation. Our FH can deliver FeGA directly to the tumor site via intratumoral injection, where it is a reservoir-based system to conserve FeGA. The photothermal properties of FeGA steadily dissolve FH under laser irradiation, and, simultaneously, FeGA reacts with a large amount of H2O2 in the cell to produce OH (Fenton reaction) which is highly toxic to mitochondria, rendering the cell inactive and reducing radiotherapy resistance. In vivo and in vitro studies suggest that combining the FH and NIR irradiation with RT (2Gy) can significantly reduce tumor proliferation without side effects such as inflammation. To conclude, this is the first study to achieve combined chemodynamic therapy (CDT) and photothermal therapy (PTT) in situ treatment, and the best therapeutic effect can be obtained with a low-dose radiation combination, thus expanding the prospects of FeGA-based tumor therapy.
Highlights
Cancer, which can strike at any age and affect anybody, is a serious threat to human life and health in society of today despite current scientific advancements (Agostinis et al, 2011; Bonfiglio et al, 2017)
We developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation
FH + NIR + RT system had the best tumor growth inhibition rate (90%), there are significant differences compared with each other experiment group, indicating that FH-mediated improved concentration of OH of tumor microenvironment (TME) can exert influence on mitochondria and enhance the RT effect to realize tumor cells growth inhibition
Summary
Cancer, which can strike at any age and affect anybody, is a serious threat to human life and health in society of today despite current scientific advancements (Agostinis et al, 2011; Bonfiglio et al, 2017). The FH can be employed as a FeGA storage controller to achieve regulated drug release and for intratumor injection of local tumor This is the first report to achieve the combined treatment of CDT and PTT in situ and that the highest therapeutic result can be obtained when low-dose radiation was used in combination. FH + NIR + RT system had the best tumor growth inhibition rate (90%), there are significant differences compared with each other experiment group, indicating that FH-mediated improved concentration of OH of tumor microenvironment (TME) can exert influence on mitochondria and enhance the RT effect to realize tumor cells growth inhibition These findings, taken together, motivate us to fully investigate anti-tumor efficacy in vivo. The in vivo results show that our unique combined treatment achieves a high level of biological safety and increases tumor OH content and enhances the efficacy of RT with a powerful FH-enhanced therapy
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