Gadolinium Polytungstate Sensitizer Modified by Chitosan

Radiotherapy (RT) is one of the most widely used methods to treat cancer in clinic. Its main principle is to inhibit the proliferation of cancer by using high intensity ionizing radiation (X-ray or gamma-ray) with very strong penetrating force.

In the course of radiotherapy, ionic radiation reacts with water or oxygen in tissues, producing a large number of cytotoxic reactive oxygen species (ROS) to induce DNA double strand damage. However, radiotherapy still faces the problem of ineffective eradication of hypoxic tumors.

Zhao Yuliang, a researcher at the Institute of High Energy Physics, Chinese Academy of Sciences, and his team have reported the use of nanomaterials containing gadolinium polytungstate as sensitizers. Gadolinium polytungstate nanoclusters were synthesized by a simple recrystallization method. These nanoclusters have very small size (~ 3.5 nm), good imaging performance of MRI and CT. At the same time, after reduction by ultraviolet lamp irradiation, the reduced products have strong absorption in the near infrared region, so they can be used as photothermal therapy reagents for tumors. In addition, gadolinium polytungstate in Gadolinium polytungstate nanomaterials can not only reduce the level of glutathione, but also achieve a good radiosensitization effect.

The process of preparing chitosan modified gadolinium polytungstate is as follows:

A gadolinium tungstate gadolinium complex modified by gadolinium tungstate and chitosan was prepared by Ion Gel method. It includes:

(A)Dissolve chitosan in acetic acid to obtain acetic acid solution of chitosan;

(B)The aqueous solution of gadolinium polytungstate was prepared by using gadolinium polytungstate crystal and water.

(C)The chitosan-modified gadolinium polytungstate was obtained by mixing the aqueous solution of gadolinium polytungstate with the acetic acid solution of chitosan to form a suspension and remove impurities.

Nano gadolinium tungstate composite nanomaterials can be obtained by using ion gelling reaction of gadolinium tungstate and chitosan.

In nanomaterials containing gadolinium polytungstate, on the one hand, gadolinium polytungstate can absorb a large number of high-energy X-rays to produce Auger or Compton electrons, which can react with water or oxygen in the organism environment (such as living cells) to produce a large number of reactive oxygen species (ROS), thereby damaging the DNA double strands of cells and achieving the effect of radiation therapy; on the other hand, gadolinium polytungstate can absorb a large number of high-energy X-rays to produce Auger or Compton electrons. On the other hand, chitosan was used to modify gadolinium polytungstate and loaded with small interfering RNA. The expression of HIF-1alpha in hypoxic tumor cells could be reduced by mediating small interfering RNA into the tumor site, which prevented the self-repair of double-stranded damaged DNA. Finally, the therapeutic effects of gadolinium polytungstate, gadolinium polytungstate gene and the expression of HIF-1alpha in cells could be achieved. The synergistic effect of surface action can enhance both internal and external sensitization, and achieve a very good radiotherapeutic effect.

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