Injectable Hydrogel for Synergetic Low Dose Radiotherapy, Chemodynamic Therapy and Photothermal Therapy

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.

Recent progress of hydrogel-based local drug delivery systems for postoperative radiotherapy

“…Ionizing radiation, which includes high-energy X-rays, gamma rays, heavy ions, as well as electrons, is used in radiotherapy to directly produce DNA damage, or indirectly induce cell death by stimulating the generation of massive numbers of toxic reactive oxygen species (ROS) ( 61 ). However, abnormal vasculature and insufficient blood flow together contribute to hypoxia in solid tumors, which significantly reduces the effectiveness of radiotherapy and leads to radiation resistance ( 62 ).…”

An Overview on Recent Progress of the Hydrogels: From Material Resources, Properties, to Functional Applications

“…In addition to the mentioned applications above, the hydrogels are widely used in other areas, such as low temperature photothermal sterilization, [259,260] skin radiation protection, [261][262][263] electrochromic displays, [264,265] and so on. In fact, with the deepening of scientific research, a class of materials called microgels has also attracted considerable attention.…”

Progress of Nanomaterials-Based Photothermal Therapy for Oral Squamous Cell Carcinoma

“…At the same time, FeGA can react with hydrogen peroxide in cells to produce hydroxyl radical (Fenton reaction), which can damage cells and reduce radiation resistance. In vitro and in vivo studies showed that the new FH nanosystem could realize the combination of low-dose radiotherapy, chemodynamic therapy, and PTT under NIR and X ray (2 Gy) irradiation [ 127 ].…”