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Cerebral glioma drug delivery system integrating three-in-one of chemotherapy, photodynamic therapy and chemodynamic therapy and preparation method of cerebral glioma drug delivery system

A technology of photodynamic therapy and glioma, applied in the field of medicine, can solve the problems of unsatisfactory treatment effect, high degree of malignancy and high mortality of glioma, achieve important scientific value and clinical prospect, and reduce the risk of recurrence , improve the effect of treatment

Pending Publication Date: 2022-03-25
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Glioma is highly malignant, the treatment effect is not ideal, the prognosis is extremely poor and the mortality rate is extremely high, the median survival time is less than 18 months, and the 5-year survival rate is less than 3%.
However, its clinical efficacy and safety are controversial, and the main disadvantages are: fast drug release; inconvenient operation (surgeons need to implant multiple chips, which can easily lead to translocation and blockage of the ventricle); serious postoperative complications (including epilepsy, intracranial abscess, meningitis, cerebrospinal leak and abnormal wound healing, etc.)

Method used

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  • Cerebral glioma drug delivery system integrating three-in-one of chemotherapy, photodynamic therapy and chemodynamic therapy and preparation method of cerebral glioma drug delivery system
  • Cerebral glioma drug delivery system integrating three-in-one of chemotherapy, photodynamic therapy and chemodynamic therapy and preparation method of cerebral glioma drug delivery system
  • Cerebral glioma drug delivery system integrating three-in-one of chemotherapy, photodynamic therapy and chemodynamic therapy and preparation method of cerebral glioma drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Synthesis of self-luminescent photosensitizer molecules (CL small molecules for short)

[0038] CL small molecules were prepared by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) / N-hydroxysuccinimide (NHS)-activated condensation reaction. Briefly, 50 mg (0.08 mmol) of Ce6 was dissolved in 10 ml of anhydrous DMSO, and EDC [236 mg (1.23 mmol)] and NHS [144 mg (1.25 mmol)] were added sequentially. The reaction mixture was stirred at 50° C. for 17 hours in the dark. Then, luminol [28 mg (0.16 mmol)] was added to the above solution. The reaction was continued, and after 3 days, the reaction was stopped, and the reaction liquid was made into sand, and separated by column chromatography (the mobile phase ratio was chloroform:methanol:formic acid=20:1:0.1), and the black solid product was obtained after the solvent was removed by rotary evaporation. That is, CL small molecule. Its structure was characterized by H NMR spectroscopy. The result is...

Embodiment 2

[0039] Example 2: Investigation of Spectroscopic Properties of CL

[0040] The UV absorption spectra and fluorescence excitation and emission spectra of luminol, Ce6 and CL were characterized by UV-Vis spectrophotometer and fluorescence spectrophotometer.

[0041] To analyze the ability of CL to produce bioluminescence resonance energy transfer (BRET) effect in vitro, Cu 2+ Slowly dropwise add H 2 o 2 CL solution, and then put it in the ultra-weak light analyzer for measurement, it is obtained that the Cu 2+Added to vary the luminescence curve. see results figure 2 shown.

Embodiment 3

[0042] Example 3: RGD-PEG 2000 -Synthesis and characterization of DSPE

[0043] Preparation of RGD-PEG via condensation of maleimide and sulfhydryl groups 2000 -DSPE, accurately weigh 10 mg of thiolated RGD polypeptide and dissolve it in 1 mL of phosphate buffer, then weigh 4 mg of Maleimide-PEG 2000 -DSPE was dissolved in 1 mL of N,N-dimethylformamide (N,N-Dimethylformamide, DMF), and the two were slowly added dropwise to 8 mL of phosphate buffer, and after magnetic stirring for 4 hours, the dialysis method (The molecular weight cut-off is 3.5kDa, and the dialysis medium is pure water) to remove DMF and unreacted thiolated RGD polypeptide, and then freeze-dry to obtain RGD-PEG 2000 -DSPE. Characterization of Maleimide-PEG by 1H NMR 2000 -DSPE and the produced RGD-PEG 2000 -DSPE. The result is as image 3 shown.

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Abstract

The invention discloses a three-in-one brain glioma drug delivery system integrating chemotherapy, photodynamic therapy and chemodynamic therapy and a preparation method of the three-in-one brain glioma drug delivery system. The drug delivery system is characterized in that RGD polypeptide modified brain glioma targeted paclitaxel prodrug nanoparticles coated with self-luminous photosensitizer molecules and copper peroxide nanodots are dispersed in a three-dimensional skeleton of a temperature-sensitive hydrogel matrix material. The system integrates three functions of chemotherapy, photodynamic therapy and chemical dynamic therapy, synergistically improves the postoperative treatment effect of glioma, and effectively reduces the postoperative recurrence risk of glioma.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a thermosensitive gel-loaded triple targeting nano-delivery system, in particular to a novel postoperative glioma treatment gel drug delivery system and a preparation method thereof. Background technique [0002] Glioma is the most common primary central nervous system (Central Nervous System, CNS) tumor, accounting for about 80% of all primary CNS tumors. Glioma has a high degree of malignancy, unsatisfactory treatment effect, extremely poor prognosis and high mortality. The median survival time is less than 18 months, and the 5-year survival rate is less than 3%. According to WHO data, glioma has become the No. 2 cancer killer for young and middle-aged people under the age of 35. At present, glioma is mainly treated with surgical resection in clinical practice. However, gliomas mostly grow in important brain functional areas, which greatly limits the scope of surgery, and glio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K31/337A61K33/34A61K41/00A61K47/60A61K47/62A61K47/36A61K47/38A61P25/00A61P35/00C01G3/02C07D305/14C08B37/08C09K11/06
CPCA61K47/60A61K47/62A61K9/06A61K9/0024A61K41/0057A61K47/38A61K47/36A61K31/337A61K33/34A61P35/00A61P25/00C01G3/02C07D305/14C09K11/06C08B37/003C09K2211/1088A61K2300/00
Inventor 辛洪亮曹想李胜男叶璐陆红丹尹昊媛
Owner NANJING MEDICAL UNIV
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