A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

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.

Oxygen-generating biocatalytic nanomaterials for tumor hypoxia relief in cancer radiotherapy

“…For example, Chen et al designed a GdW 10 @PDA-CAT (polydopamine, PDA) composite as a radiosensitizer for tumor microenvironment (TME)-regulated RT enhancement. 52 The loaded CAT in the nanocomposite could catalyze the decomposition of H 2 O 2 to H 2 O and oxygen to enhance the RT efficacy under hypoxic TME. The loaded CAT and PDA modification could also improve the biocompatibility of the nanocomposites.…”

Nanofabrications of Erythrocyte Membrane-Coated Telmisartan Delivery System Effective for Radiosensitivity of Tumor Cells in Mice Model

“… 11 Most current research focused on increasing the local oxygen content of the tumor through exogenous oxygen-carrying or catalytic oxygen production agents or combined with the introduction of high atomic number materials to absorb more radiation energy and enhance the local radiation energy in cells for radiosensitization. 12–14 Sang et al 13 increased the oxygen content in the tumor by carrying hemoglobin in the carrier to enhance the efficacy of radiotherapy. Pei et al 14 prepared a nano-oxygen generator based on metal-organic framework and Au-Pt composite material, which can effectively catalyze the decomposition of H 2 O 2 at the tumor site to generate O 2 and cooperate with the radiation energy enhancement effect of high atomic number Au and Pt to promote radiosensitization.…”

Hypoxia-Responsive Aggregation of Gold Nanoparticles for Near-Infrared-II Photoacoustic Imaging-Guided Enhanced Radiotherapy

“…In clinical practice, RT is used in different phases of treatment for 60–70% of patients with malignant tumors . Unfortunately, the therapeutic use of RT in cancer treatment is severely constrained by radioresistance brought on by intratumoral hypoxia and the toxicity of high-dose radiation for surrounding healthy tissues. − It is well known that hypoxia is one of the defining characteristics of most solid tumors and an important cause of cancer progression and poor prognosis. − During RT, the hypoxic environment reduces the production of ROS and cytotoxic substances. , In addition, reducing substances, including sulfhydryl-containing molecules within the tumor, can significantly reduce the ionizing damage to the genomic DNA of cancer cells caused by ionizing radiation. − To address these issues, a variety of radiosensitizers that attempt to increase the radiation sensitivity of cancer cells have been developed and used in clinical settings, including sodium glycidazole and nimozole. − However, due to the low bioavailability in the body, large doses of sensitizers are required to achieve satisfactory radiosensitization effects, leading to serious negative impacts on healthy tissues, organs, and the central nervous system. High-atomic-number (high-Z) metals have received a lot of interest in the field of radiosensitization because they can greatly enhance the attenuation of X-rays and facilitate the deposition of radiation energy within the tumor. − To date, many nanoplatforms containing high-Z elements for radiosensitization have been successfully developed. − However, most of the current nanomedicines are unable to penetrate tumors and cannot reach cancer cells located far from the tumor-associated blood vessels, especially in the hypoxic area.…”