Preparation method and application of platinum peptide copolymer with siRNA transportation function

A copolymer and functional technology, applied in the field of biomedical applications, can solve problems such as leakage, affecting the size of the carrier structure, load capacity, side effects, etc., to achieve the effects of reducing losses, avoiding non-specific leakage, and reducing side effects

Pending Publication Date: 2022-03-22
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since chemotherapeutic drugs and functional genes cannot be independently loaded into nanoparticles, which affects the size of the carrier structure and its loading capacity, at the same time, due to the interference between molecules, non-specific leakage of genes and drug molecules may also occur. Unnecessary side effects during systemic circulation

Method used

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  • Preparation method and application of platinum peptide copolymer with siRNA transportation function
  • Preparation method and application of platinum peptide copolymer with siRNA transportation function
  • Preparation method and application of platinum peptide copolymer with siRNA transportation function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1: Solid phase synthesis of polypeptide KRKRKR (Lys-Arg-Lys-Arg-Lys-Arg)

[0050] 1a. Weigh 500mg Rink Amide MBHA resin, add DMF (N,N-dimethylformamide) to swell for 1h; add 5ml 20% piperidine / DMF solution to react for 10min, then wash with DMF solution 4 times; add 700mgFomc-Lys (Boc)-OH, 180mg 1-hydroxybenzotriazole (HOBT), 520mg benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and 450ul N,N -Diisopropylethylamine (DIEA), dissolved in DMF for 12 hours, washed with DMF; then carried out to detect the amino group with ninhydrin, showing that it did not turn blue, indicating that the connection was successful; adding 8ml of 20% piperidine / DMF solution to react for 10min, and This step (adding 8ml of 20% piperidine / DMF solution to react for 10min) was repeated once, washed with DMF, and then carried out ninhydrin to detect the amino group, and the display turned blue, indicating that the deprotection was successful.

[0051] 1b. Add 750mg ...

Embodiment 2

[0054] Embodiment 2: the synthesis of tetravalent carboxyplatinum

[0055] 2a. Weigh 100mg of cisplatin into a 50ml round bottom flask, then add 7-8ml of 30% H 2 o 2 Solution, stirred and reacted for 4 hours at 75°C in the dark; to complete the reaction, remove most of the solvent by rotary evaporation, then cool overnight, collect the precipitate, wash with acetone and ether for 1-2 times, and freeze-dry to obtain hydroxyplatinum;

[0056] 2b. Weigh 100mg of hydroxyplatinum and 120mg of succinic anhydride into a 50ml round bottom flask, add 3-5ml of DMF, and stir at 50°C in the dark for 24h; end the reaction, remove the solvent by lyophilization, dissolve with a little acetone, add ether dropwise to precipitate out , the precipitate was collected, washed with ether three times, and freeze-dried to obtain the tetravalent carboxyplatinum product Pt(IV)-COOH.

Embodiment 3

[0057] Embodiment 3: the synthesis of platinum peptide cross-linked product Pt-AA

[0058] Weigh 74 mg of the polypeptide KRKRKR and dissolve it in 15 ml of 100 mM PBS with pH=7.4, then add 2 times the molar amount (calculated as the polypeptide) of Pt(IV)-COOH, 8 times the molar amount (calculated as the polypeptide) of NHS and 20 times the molar amount ( Calculated by polypeptide) EDCI was dissolved in 5ml water and reacted for 30min, then the two solutions were mixed evenly, stirred at room temperature in the dark for 12h, after lyophilization, the solvent was removed, firstly purified with chloroform and acetone to remove organic small molecule impurities, and then passed through gel chromatography The column removes impurities to obtain the platinum peptide cross-linked product Pt-AA.

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Abstract

The invention discloses a preparation method and application of a platinum peptide copolymer with a function of transporting siRNA (small interfering ribonucleic acid), carboxyl platinum with an anti-tumor effect is used as a cross-linked molecule, polypeptide containing arginine and lysine is cross-linked to form the platinum peptide copolymer, and then the platinum peptide copolymer is mixed and assembled with siRNA capable of inducing apoptosis by utilizing electrostatic interaction to obtain the platinum peptide copolymer with the function of transporting siRNA. And finally, wrapping with negatively charged lipidosome to form a stable nano compound, and finally preparing the nano delivery system for chemical/gene synergistic therapy. The nano delivery system solves the problems that the treatment effect of a single therapy is poor and siRNA is easy to degrade or clear in the process of reaching tumors, and has the advantages of water solubility, good dispersity, high stability, good biocompatibility and the like.

Description

technical field [0001] The invention belongs to the field of biomedical applications, and in particular relates to a preparation method and application of a platinum peptide copolymer capable of transporting siRNA. Background technique [0002] In today's society, cancer is a disease that seriously endangers human health and life. Chemotherapy is currently one of the most commonly used and effective methods of cancer treatment. Among all kinds of chemotherapeutic drugs, platinum drugs are widely used in clinical treatment because of their broad anticancer spectrum and good therapeutic effect, especially cisplatin and its derivatives. However, Pt(II) drugs are easily inactivated in the cytoplasmic environment, thereby affecting their therapeutic effects. Pre-oxidized Pt(IV) complexes are considered to be an effective way to solve this problem, and can be introduced at their axial positions. New groups, more possibilities for chemical modification. [0003] RNA interference...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/65A61K9/127A61K31/7105A61P35/00B82Y5/00B82Y40/00C12N15/113C07K7/06A61K31/282
CPCA61K31/7105A61K47/65A61K31/282A61K9/127A61P35/00B82Y5/00B82Y40/00C12N15/113C07K7/06C12N2310/141
Inventor 李麦云刘扬中
Owner UNIV OF SCI & TECH OF CHINA
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