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CN-121971605-A - Ultrasonic sensitizer for preparing iron-titanium metal organic framework for treating pancreatic cancer and application of ultrasonic sensitizer

CN121971605ACN 121971605 ACN121971605 ACN 121971605ACN-121971605-A

Abstract

The invention belongs to the technical field of ultrasonic therapy sensitizers, and relates to an iron-titanium metal organic framework ultrasonic sensitizer for preparing a medicine for treating pancreatic cancer and application thereof. The invention discloses an iron-titanium metal organic frame ultrasonic sensitizer for preparing a medicine for treating pancreatic cancer, which is prepared by adding an iron metal compound and an organic ligand into a mixed organic solution, uniformly mixing, carrying out hydrothermal reaction for 1-24 h at 50-130 ℃, then adding a titanium metal compound, and carrying out hydrothermal reaction for 12-48 h at 135-200 ℃, wherein the application process of the iron-titanium metal organic frame ultrasonic sensitizer for preparing the medicine for treating pancreatic cancer comprises the steps that under ultrasonic irradiation, the iron-titanium metal organic frame ultrasonic sensitizer for preparing the medicine for treating pancreatic cancer acts on pancreatic cancer cells, and the cell survival rate is less than or equal to 20%. The invention also discloses a medicine for treating pancreatic cancer, which comprises the iron-titanium metal organic framework ultrasonic sensitizer.

Inventors

  • XIE CHAOXIANG
  • REN WENZHI
  • WU DAN
  • WU AIGUO

Assignees

  • 浙江工业大学
  • 中国科学院宁波材料技术与工程研究所
  • 宁波慈溪生物医学工程研究所

Dates

Publication Date
20260505
Application Date
20251224

Claims (10)

  1. 1. An ultrasonic sensitizer of an iron-titanium metal organic framework for preparing a medicine for treating pancreatic cancer, which is characterized in that the preparation method of the ultrasonic sensitizer of the iron-titanium metal organic framework for preparing the medicine for treating pancreatic cancer comprises the following steps: adding an iron metal compound and an organic ligand into a mixed organic solution, uniformly mixing, carrying out hydrothermal reaction for 1-24 hours at 50-130 ℃, then adding a titanium metal compound, and carrying out hydrothermal reaction for 12-48 hours at 135-200 ℃ to obtain the iron-titanium organic framework ultrasonic sensitizer for preparing the pancreatic cancer treatment medicament, wherein the molar ratio of Fe to Ti in the iron metal compound and the titanium metal compound is 1 (1-8); the application process of the ultrasonic sensitizer of the iron-titanium metal organic framework for preparing the medicine for treating pancreatic cancer comprises the step that under ultrasonic irradiation, the ultrasonic sensitizer of the iron-titanium metal organic framework for preparing the medicine for treating pancreatic cancer acts on pancreatic cancer cells, and the cell survival rate is less than or equal to 20 percent.
  2. 2. The ultrasonic sensitizer of an iron-titanium metal organic framework for preparing a medicine for treating pancreatic cancer according to claim 1, wherein the molar ratio of Fe to Ti in the iron metal compound and the titanium metal compound is 1:4.
  3. 3. The ultrasonic sensitizer of an iron-titanium metal organic framework for preparing a medicine for treating pancreatic cancer according to claim 1, wherein the ratio of the sum of the molar amounts of Fe and Ti in the iron metal compound and the titanium metal compound to the molar amount of the organic ligand is 1 (2-8).
  4. 4. The ferric-titanium metal organic framework ultrasound sensitizer for the preparation of a medicament for the treatment of pancreatic cancer according to claim 1, wherein the ferric metal compound comprises one or more of ferric chloride, ferric sulfate, ferric nitrate, ferrous chloride, ferrous sulfate and ferrous nitrate; The organic ligand comprises one or more of porphyrin ligand, carboxylic acid ligand, phthalic acid, terephthalic acid, phthalic acid, 1, 4-phthalic acid, p-hydroxybenzoic acid, pyridine and derivatives thereof, 1, 4-benzene dicarboxylic acid, benzene tricarboxylic acid, benzene tetracarboxylic acid, benzene dicarboxylic acid, benzene hexa-carboxylic acid, 1,3, 5-tricarboxylic acid benzene, glycine, phenylalanine, aromatic diol ligand, non-aromatic diol ligand and aromatic diamine ligand; the titanium metal compound comprises one or more of tetrabutyl titanate, tetraisopropyl titanate, tetraethyl titanate, titanium acetylacetonate, titanium benzoylacetonate and titanium acetate.
  5. 5. The ultrasonic sensitizer of the iron-titanium metal organic frame for preparing the medicine for treating the pancreatic cancer according to claim 1, wherein the intensity of ultrasonic irradiation is 0.5-2W, the frequency is 1-10 MHz, and the duty ratio is 30-70%.
  6. 6. The ultrasonic sensitizer of the Fe-Ti metal organic frameworks for preparing the medicines for treating the pancreatic cancer according to claim 1, wherein the application process of the ultrasonic sensitizer of the Fe-Ti metal organic frameworks for preparing the medicines for treating the pancreatic cancer comprises the steps of applying ultrasonic irradiation with the intensity of 1W, the frequency of 1MHz and the duty ratio of 50%, wherein the ultrasonic sensitizer of the Fe-Ti metal organic frameworks with the concentration of 100 mug/mL acts on pancreatic cancer cells, and the cell survival rate is less than or equal to 20%.
  7. 7. A medicament for treating pancreatic cancer, which is characterized by comprising 0.01-100 wt% of the iron-titanium metal organic framework ultrasound sensitizer for preparing the medicament for treating pancreatic cancer according to any one of claims 1-6.
  8. 8. The pancreatic cancer treatment drug according to claim 7, wherein the pancreatic cancer treatment drug comprises an iron-titanium metal-organic framework ultrasound sensitizer for preparing pancreatic cancer treatment drug at a concentration of 0.1-5 mg/mL.
  9. 9. The pancreatic cancer treatment drug according to claim 7, wherein the preparation method of the iron-titanium metal organic framework ultrasonic sensitizer for preparing the pancreatic cancer treatment drug comprises the steps of dissolving the iron-titanium metal organic framework ultrasonic sensitizer for preparing the pancreatic cancer treatment drug in a solvent to obtain the pancreatic cancer treatment drug with the concentration of 0.1-5 mg/mL.
  10. 10. The pancreatic cancer treatment drug according to claim 7, wherein the application of the pancreatic cancer treatment drug comprises applying ultrasonic irradiation with the intensity of 1W, the frequency of 1MHz and the duty cycle of 50% for 5min, and the inhibition rate of the pancreatic cancer treatment drug with the concentration of 0.1-5 mg/mL to pancreatic cancer cells is more than 80%.

Description

Ultrasonic sensitizer for preparing iron-titanium metal organic framework for treating pancreatic cancer and application of ultrasonic sensitizer Technical Field The invention belongs to the technical field of ultrasonic therapy sensitizers, and relates to an iron-titanium metal organic framework ultrasonic sensitizer for preparing a medicine for treating pancreatic cancer and application thereof. Background Pancreatic cancer is one of the most lethal malignant tumors worldwide, and its therapeutic targets are to achieve radical resection of the tumor, control local progression, delay distant metastasis, and maintain patient quality of life. Surgery is the core means of potentially curing pancreatic cancer, but the proportion of resectable cases is low and the risk of postoperative recurrence and metastasis is extremely high. Ultra-intense focused ultrasound (HIGH INTENSITY Focused Ultrasound, HIFU) precisely focuses low-energy ultrasound in vitro on a tumor site, and generates instantaneous high temperature at a focal point by utilizing the thermal effect of ultrasound, thereby causing coagulation necrosis of tissues. Currently, HIFU achieves a certain effect in the treatment of prostate cancer, pancreatic cancer, liver cancer and the like. However, in the clinical application process, the problem that the tumor ablation is incomplete and the normal tissues are not clearly damaged by the tumor boundary identification still exists. The acoustic power treatment (Sonodynamic therapy, SDT) is a noninvasive tumor treatment technology, uses ultrasonic energy to activate an ultrasonic sensitizer in a tumor, directly destroys a cell structure by generating physical mechanical force through an acoustic cavitation effect, triggers an sonochemical reaction to generate a large amount of active oxygen (ROS) with strong cytotoxicity, and thus efficiently kills tumor cells, and realizes an accurate treatment effect. The early research of the ultrasonic sensitizer is porphyrin and derivatives thereof, and now some inorganic nano materials based on gold, titanium dioxide, ferric oxide, manganese dioxide and the like start to be researched in the field of acoustic power treatment by virtue of good stability and biocompatibility, and the inorganic semiconductor nano particles are excited to transition to a conduction band by electrons on a valence band under the action of ultrasonic waves, so as to form electron-hole pairs, different from an energy transition mechanism generated by sonoluminescence of the organic sensitizer. The electrons and holes with high energy have strong reducing and oxidizing capacities and can generate ROS, but most inorganic sound sensitizer materials have wide forbidden bands, the band gaps are high, the required excitation energy threshold is large, the electron-hole recombination is fast, the service life of carriers is short, the ROS yield is low, and the sound power treatment sensitization effect is severely limited. How to design a novel ultrasonic sensitizer, reduce the excitation threshold of band gap and reduce ultrasonic energy, improve the ROS generating capacity of ultrasonic excitation, and is a great problem for realizing the high-efficiency acoustic power treatment of pancreatic cancer. Disclosure of Invention The invention aims at solving the problems in the prior art and provides an iron-titanium metal organic framework ultrasonic sensitizer for preparing a medicine for treating pancreatic cancer and application thereof. One object of the invention is achieved by the following technical scheme: An ultrasonic sensitizer of an iron-titanium metal organic framework for preparing a medicine for treating pancreatic cancer, the preparation method comprises the following steps: adding an iron metal compound and an organic ligand into a mixed organic solution, uniformly mixing, carrying out hydrothermal reaction for 1-24 hours at 50-130 ℃, then adding a titanium metal compound, and carrying out hydrothermal reaction for 12-48 hours at 135-200 ℃ to obtain the iron-titanium organic framework ultrasonic sensitizer for preparing the pancreatic cancer treatment medicament, wherein the molar ratio of Fe to Ti in the iron metal compound and the titanium metal compound is 1 (1-8); the application process of the ultrasonic sensitizer of the iron-titanium metal organic framework for preparing the medicine for treating pancreatic cancer comprises the step that under ultrasonic irradiation, the ultrasonic sensitizer of the iron-titanium metal organic framework for preparing the medicine for treating pancreatic cancer acts on pancreatic cancer cells (Panc-2 cells), and the cell survival rate is less than or equal to 20%. Preferably, the molar ratio of Fe to Ti in the iron metal compound to the titanium metal compound is 1:4. Further preferably, the ultrasonic sensitizer of the iron-titanium metal organic framework is a nanosheet, the average size of the nanosheet is 100-500 nm, and the thickness of the