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Abstract
Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.
Highlights
IntroductionRadiation therapy (RT), is one of the most commonly used treatments to inhibit tumor growth [1]
Hypoxic-Tumor Radiotherapy.Radiation therapy (RT), is one of the most commonly used treatments to inhibit tumor growth [1]
Our study has demonstrated that using high-Z effects and self-supplied oxygen is an excellent strategy to improve tumor radiotherapy
Summary
Radiation therapy (RT), is one of the most commonly used treatments to inhibit tumor growth [1]. As many as 40% of tumors develop resistance to radiation therapy, significantly complicating treatment [2]. Tumor hypoxia is one of the important causes of radiation resistance [3]. The presence of hypoxic cells in tumor tissues is an important factor to reduce the effects of radiation exposure [4]. Tumor tissue often has problems of insufficient blood supply and a high ratio of hypoxic cells, and some cancer cells can escape radiation damage, which is one of the common reasons for tumor recurrence after radiotherapy [7]. Hypoxic cells in tumor tissues are resistant to chemoradiotherapy, and they continue to maintain survival function by anaerobic glycolysis. After the hypoxic state is improved, they can divide and proliferate, which becomes the root of tumor recurrence and metastasis in the future [8]
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