Targeted cell-penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, modified nanoparticle compound and pharmaceutical application

A nanoparticle and membrane-penetrating peptide technology, applied in nanomedicine, nanotechnology for materials and surface science, nanotechnology, etc., can solve the problems of high cytotoxicity, lack of targeting, etc., to prolong circulation time, improve Colloid stability and enhanced radiosensitivity effects

Pending Publication Date: 2021-07-30
SECOND AFFILIATED HOSPITAL OF COLLEGE OF MEDICINEOF XIAN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the main bottleneck affecting the application of PEI is its high cytotoxicity and lack of targeting

Method used

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  • Targeted cell-penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, modified nanoparticle compound and pharmaceutical application
  • Targeted cell-penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, modified nanoparticle compound and pharmaceutical application
  • Targeted cell-penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, modified nanoparticle compound and pharmaceutical application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Synthesis of R9-SSPEI-lncGAS nanoparticle complex

[0031] see figure 1 , the specific synthesis process is as follows:

[0032]The synthesized lncGAS was dissolved in a flask (100ml) with methanol (30ml), and the sample was purified with liquid nitrogen and stored in vacuum for 10-20min. The calculated amount of propylene sulfide (1.2k 5 moles more than BPEI) was added by syringe. The solution was stirred at 60°C for 24 h, and the reaction mixture was evaporated to dryness under reduced pressure, then dissolved in methanol, and precipitated twice in ice-cold diethyl ether. Ellman's method was used to measure the content of thiol groups in the product. BPEI-SH (0.5 g) was dissolved in anhydrous dimethyl sulfoxide (50 ml), and stirred at room temperature for 48 h to cause oxidative cross-linking of thiol groups. The product was purified by dialysis against D.I. water (mwco3500) and extensively freeze-dried, and its chemical structure was confirmed by proton...

Embodiment 2

[0034] Example 2 Stability detection of R9-SSPEI-lncGAS nanoparticle complex

[0035] The stability of the nanocomplexes was determined by qRT-PCR experiments ( figure 2 ). 50nM R9-SSPEI / lncGAS nanoparticle complex and 50nM lncGAS (control) were incubated with serum at 37°C, and samples at different time points were taken for qRT-PCR to observe the stability of lncGAS.

Embodiment 3

[0036] Example 3 Cytotoxicity detection of R9-SSPEI-lncGAS nanoparticle complexes

[0037] MTT assay was performed after adding different mass ratios of R9-SSPEI / lncGAS complexes (R9-SSPEI / lncGAS mass ratios were 0.5, 1, 2, 4, 8, 16) to cervical cancer cell lines Hela and Siha cells and incubated for 48 hours , to detect cell proliferation, such as image 3 shown.

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Abstract

The invention discloses a targeted cell-penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, a modified nanoparticle compound and pharmaceutical application. The targeted cell-penetrating peptide can specifically and efficiently enter the cervical cancer, and by regulating and controlling a PI3K / AKT pathway and playing a role of microRNA 'molecular sponge', the radiotherapy sensitivity is improved, and the radiotherapy side effect is reduced. According to the invention, PEI is modified by a micromolecular disulfide bond (-SS-), so that the toxicity of PEI is greatly reduced; meanwhile, the colloidal stability of the PEI-nucleic acid compound is also improved, and the circulation time of the PEI-nucleic acid compound in vivo is prolonged; and meanwhile, the tumor targeting polypeptide R11 is used for modifying the PEI-nucleic acid compound, so that the targeting problem of the nanoparticles in gene therapy research is solved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a targeted penetrating peptide for enhancing radiotherapy sensitivity of cervical cancer, a modified nanoparticle compound and pharmaceutical applications. Background technique [0002] Cervical cancer is one of the common malignant tumors in gynecology, and its mortality rate is second only to breast cancer, which seriously threatens women's health. The comprehensive treatment of surgery combined with radiotherapy and chemotherapy is currently the main means of cervical cancer treatment, and its curative effect has also been unanimously recognized internationally. However, about 13% of cervical cancer patients who received radiation therapy still experienced local recurrence. A large part of this is due to the occurrence of radiotherapy resistance in the tumor, and because the molecular mechanism of radiotherapy resistance is still unclear, it is difficult to accurately predi...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K47/64A61K41/00A61K48/00A61K38/17A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCC07K7/06A61K47/64A61K41/0038A61K48/005A61K48/0025A61K38/1709A61P35/00B82Y5/00B82Y30/00B82Y40/00
Inventor 赵艳张婷婷段钊师蕊婷
Owner SECOND AFFILIATED HOSPITAL OF COLLEGE OF MEDICINEOF XIAN JIAOTONG UNIV
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