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CN-122005848-A - Gel for preventing radiodermatitis

CN122005848ACN 122005848 ACN122005848 ACN 122005848ACN-122005848-A

Abstract

The invention discloses a gel for preventing radiodermatitis. The invention designs iNOS-DNase, and the nucleotide sequence of the iNOS-DNase is shown as SEQ ID NO. 1. Dissolving the iNOS-DNase and cobalt nitrate in methanol to obtain a solution A, dissolving the dimethylimidazole in methanol to obtain a solution B, mixing and stirring the solution A and the solution B to obtain iNOS-DZ@ZIF-67, dissolving hyaluronic acid in a sodium acetate solution to obtain a Hyaluronic Acid (HA) solution, adding the iNOS-DZ@ZIF-67/HA into the solution, stirring the solution in a dark place, freeze-drying the precipitate, and adding water to mix the solution when in use to obtain the gel for preventing radiodermatitis. The gel prepared by the invention has good stability, slow release property and angiogenesis effect, can improve the delivery rate and antibacterial property, and can be used for targeted prevention and treatment of radiodermatitis.

Inventors

  • LI DONG
  • ZHOU DAIJUN
  • Bao Lingbo
  • LI ZHIHUI

Assignees

  • 中国人民解放军西部战区总医院

Dates

Publication Date
20260512
Application Date
20260209
Priority Date
20260205

Claims (10)

  1. 1. A gel for preventing radiodermatitis, prepared by the method of: (1) Dissolving iNOS-DNase and cobalt nitrate in methanol to obtain solution A, dissolving dimethyl imidazole in methanol to obtain solution B, mixing the solution A and the solution B, stirring, centrifuging, washing to obtain precipitate, and lyophilizing the precipitate to obtain iNOS-DZ@ZIF-67; (2) Dissolving hyaluronic acid in a sodium acetate solution to obtain a hyaluronic acid solution, adding iNOS-DZ@ZIF-67, stirring in a dark place, centrifuging, washing to obtain a precipitate, lyophilizing the precipitate to obtain iNOS-DZ@ZIF-67/HA, and dissolving the iNOS-DZ@ZIF-67/HA in water to obtain the gel for preventing radiodermatitis.
  2. 2. The gel of claim 1, wherein in step (1), the nucleotide sequence of iNOS-dnase is shown in SEQ ID No. 1.
  3. 3. The gel according to claim 1, wherein in the step (1), the addition amount ratio of the cobalt nitrate, iNOS-dnase and methanol is (0.7-0.8) g/50 mL, and the concentration of the dimethylimidazole in the solution B is 0.03-0.035 g/mL.
  4. 4. The gel of claim 1, wherein in step (1), the volume ratio of the solution A to the solution B is 1:1, and the stirring time is 8 hours.
  5. 5. The gel of claim 1, wherein in step (1), the washing is 3 times with methanol, the lyophilization temperature is-20 ℃, and the lyophilization time is 2 hours.
  6. 6. The gel according to claim 1, wherein in the step (2), the concentration of the sodium acetate solution is 0.2M, the concentration of the hyaluronic acid solution is 2mg/mL, and the ratio of the addition amount of iNOS-DZ@ZIF-67 to the addition amount of the hyaluronic acid solution is 10 mg/10 mL.
  7. 7. The gel of claim 1, wherein in step (2), the light-protected agitation is for a period of 24 hours.
  8. 8. The gel of claim 1, wherein in step (2), the washing is 3 times with methanol, the lyophilization temperature is-20 ℃ and the lyophilization time is 2 hours.
  9. 9. The gel according to claim 1, wherein in the step (2), iNOS-dz@zif-67/HA and water are mixed in a ratio of 1mg to 1ml, and the iNOS-dz@zif-67/HA is dissolved in water to obtain the gel for preventing radiodermatitis.
  10. 10. Use of a gel according to any one of claims 1 to 9 for increasing iNOS-DZ delivery rate or for the preparation of a product for the treatment of radiodermatitis.

Description

Gel for preventing radiodermatitis Technical Field The invention relates to the technical field of biological medicine, in particular to gel for preventing radiodermatitis. Background Radiodermatitis (Radiation dermatitis, RD) is an acute and chronic injury caused by irradiation of skin with various types of ionizing radiation such as alpha, beta, gamma, X-rays, etc., and the incidence rate of RD in radiotherapy patients is as high as 90% or more, which can also occur in radioprofessional exposure, radiological accidents, nuclear warfare, etc. Therefore, how to prevent RD has become a hot spot and difficult problem to be solved in the field of radioprotection. In recent years, biological materials with safe, effective, and economical characteristics have become new hot spots for preventing RD. In the development of radiodermatitis, inducible Nitric Oxide Synthase (iNOS) plays a central pathological driving role. The mechanism is that ionizing radiation can activate signal channels including NF- κB while directly damaging skin cell DNA and inducing oxidative stress, and induce epidermal keratinocyte and infiltrated immune cells to express iNOS. Thus, excessive activation of iNOS, which extends the entire process from early injury, inflammation amplification to repair delay of radiodermatitis, becomes a core molecular bridge connecting radiation physical injury and complex biological lesions. However, few treatments for inflammation using iNOS are currently reported. Dnase (DZ) refers to a single-stranded DNA sequence with catalytic activity, obtained by in vitro artificial design and screening, which can cleave RNA-based viruses or act as a gene silencing molecule in diseases with elevated expression levels of non-coding RNAs or certain proteins. However, current studies on iNOS-dnase are still blank. The DNase (DZ) can cut specific mRNA in a targeted manner, as the patent of application number CN 118340716A discloses a miR155/iNOS-DZ@CuTz-1 biogel, a preparation method and application thereof, iNOS-DZ can degrade iNOS, meanwhile, a connection signal miR155, cuTz-1 is a monodisperse copper-based metal-organic framework material, oxygen can be loaded, local hypoxia of skin can be relieved, over-expressed glutathione can be cleared, oxidative stress reaction can be reduced, and the miR155/iNOS-DZ can be entrapped, and the prepared miR155/iNOS-DZ@CuTz-1 biogel can effectively promote wound healing of a radioactive dermatitis mouse. miR-155 is a typical inflammation-related miRNA, and is upregulated by a plurality of inflammations, infections, immune activation and tissue injury, so that when miR-155 is used as a 'radiodermatitis early-stage specific signal', skin inflammation (such as infection, friction stimulus, allergic dermatitis and the like) which is not subjected to radiation injury can be triggered, and the premature release/excessive release of materials can be caused. However, iNOS-dnase alone is easily inactivated, difficult to deliver and single-function. Therefore, how to treat radiodermatitis using iNOS-dnase and to improve the delivery rate and antibacterial property, and to improve the effect of treating radiodermatitis is a problem to be solved. Disclosure of Invention In view of the above prior art, it is an object of the present invention to provide a gel for the prevention of radiodermatitis. The invention designs an iNOS-DNase, which is encapsulated in ZIF-67, and the ZIF-67 is externally connected with hyaluronic acid to obtain gel for preventing radiodermatitis. The gel has good stability, slow release property and angiogenesis effect, can improve delivery rate and antibacterial property, and can be used for targeted prevention and treatment of radiodermatitis. In order to achieve the above purpose, the invention adopts the following technical scheme: in a first aspect of the invention, there is provided a gel for the prevention of radiodermatitis, prepared by the method of: (1) Dissolving iNOS-DNase and cobalt nitrate in methanol to obtain solution A, dissolving dimethyl imidazole in methanol to obtain solution B, mixing the solution A and the solution B, stirring, centrifuging, washing to obtain precipitate, and lyophilizing the precipitate to obtain iNOS-DZ@ZIF-67; (2) Dissolving hyaluronic acid in a sodium acetate solution to obtain a hyaluronic acid solution, adding iNOS-DZ@ZIF-67, stirring in a dark place, centrifuging, washing to obtain a precipitate, lyophilizing the precipitate to obtain iNOS-DZ@ZIF-67/HA, and dissolving the iNOS-DZ@ZIF-67/HA in water to obtain the gel for preventing radiodermatitis. Preferably, in the step (1), the nucleotide sequence of the iNOS-DNase is shown as SEQ ID NO. 1: GGCAAGCCAGGCTAGCTACAACGAGTCTGAGAC. Preferably, in the step (1), the addition amount ratio of the cobalt nitrate, the iNOS-DNase and the methanol is (0.7-0.8) g, 0.25mg and 50mL, and the concentration of the dimethylimidazole in the solution B is 0.03-0.035 g/mL. Preferably, in the step (1