Strong oncolytic rod-shaped nano-assembly, preparation method and application thereof

A nano-assembly, oncolytic technology, applied in the field of medical biomaterials, can solve problems such as toxic and side effects of healthy tissues, and achieve the effects of increasing tumor enrichment, enhancing cell entry efficiency and oncolytic effect, and improving the effect of membrane rupture.

Pending Publication Date: 2020-01-10
NANJING IND INST FOR ADVANCED INTELLIGENT EQUIP
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Moreover, the current nano-drug delivery system often has toxic and side effects on healthy tissues, so it can only be activated at the tumor site, and particles that produce "oncolytic" effects have gradually entered the public's field of vision.

Method used

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  • Strong oncolytic rod-shaped nano-assembly, preparation method and application thereof
  • Strong oncolytic rod-shaped nano-assembly, preparation method and application thereof
  • Strong oncolytic rod-shaped nano-assembly, preparation method and application thereof

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preparation example Construction

[0041] The present invention provides an oncolytic rod-shaped supramolecular assembly, such as figure 1 , and the construction method, the oncolytic rod-shaped supramolecular assembly has a multifunctional combined strong oncolytic effect, such as figure 2 shown. Preparation method, concrete steps are as follows:

[0042] (1) Preparation of oncolytic monomers of peptide dendrimers

[0043] (2) After oxidizing and breaking the single-walled carbon nanotubes to prepare short carbon nanotubes (~300nm) with a relatively uniform length, modify Arg-Gly-Asp for targeting.

[0044] Take the oncolytic monomer (10n equivalent) in step (1) and the single-walled carbon nanotubes (1n equivalent) in step (2), dissolve them in a good solvent (DMSO), drop them into deionized Water, through hydrophilic-hydrophobic self-assembly and π-π stacking, the hydrophobic anti-tumor drug at the end of the fan-shaped oncolytic monomer drives the self-assembly of the oncolytic monomer to the surface of...

Embodiment 1

[0045] Example 1: Preparation of oncolytic monomers of peptide dendrimers

[0046] Modification of residues with the function of cell membrane penetration: arginine is selected as the membrane-penetrating functional group, and is coupled to the periphery of the peptide dendrimer skeleton through a covalent bond. Accurately weigh 3.0 g of second-generation lysine, 11.62 g of Boc-protected and pdf lysine, 11.83 g of benzotriazol-1-yl-oxytripyrrolidinylphosphonium hexafluorophosphate (PyBop) and 3.04 g of 1 -Hydroxybenzotriazole (HOBT) was dissolved in a single-necked bottle with a branch tube, N,N-dimethylamide (DMF) was added under nitrogen atmosphere, and 12.14mL N,N-diisopropylethyl Amine (DIPEA). After reacting at room temperature for 24 hours, the reaction solution was washed, dried, concentrated, purified and separated by column chromatography, and hydrazine hydrate was modified at the end of lysine (coupling tert-butoxycarbonylhydrazine Boc-NHNH 2 ), the condensation re...

Embodiment 2

[0049] Example 2: Preparation of rod-shaped prodrug self-delivery system

[0050] Take 10 mg residue-shielded oncolytic monomer and 2 mg target-modified carbon nanotubes and dissolve them in 200 μL of good solvent dimethyl sulfoxide. Under ultrasonic conditions, the above solution was dropped into 1800 μL deionized water for self-assembly. Under the hydrophobic interaction and π-π stacking, the self-assembled rod-shaped supramolecular assembly was formed, and the organic solvent was removed by dialysis (MWCO 100KDa). The rod-shaped supramolecular assembly is collectively referred to as R-SAPs.

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Abstract

The present invention provides a strong oncolytic rod-shaped nano-assembly and a preparation method thereof. Oncolytic monomers of dendritic peptide molecules are constructed. The oncolytic monomers comprise chemotherapeutic drugs connected by sensitive bonds and residues peripherally modified with oncolytic effects, and the residues are covered with a negatively charged shielding layer; the oncolytic monomers are induced to self-assemble on inner cores and closely arranged on surfaces of the inner cores to form the rod-shaped nano-assembly; or the rod-shaped nano-assembly is directly stackedthrough an organic molecular design. The provided rod-shaped supramolecular assembly morphology affects biological behaviors of particles, has advantages of prolonging blood drug circulation time, increasing tumor enrichment, improving solid tumor penetration ability, increasing cell uptake and special subcellular organelle enrichment, etc., and greatly increases anti-tumor effects.

Description

technical field [0001] The invention belongs to the field of medical biomaterials, and in particular relates to a method for preparing an oncolytic rod-shaped nano assembly and its application in reversing multidrug-resistant tumors. Background technique [0002] Supramolecular self-assemblies are widely used in antitumor research. Nanoscale particles can be passively targeted to tumor tissue through the high permeability and retention effect (EPR effect) of solid tumors or actively targeted to tumor tissue through surface-modified targeting molecules, which greatly improves the delivery efficiency of drugs and is widely used. used in antitumor therapy. [0003] Factors affecting tumor delivery efficiency include: particle size, morphology, surface charge, etc. Among them, particle morphology is considered to be one of the most critical properties in the internalization process. Most of the existing supramolecular assemblies are spherical nanoparticles, and many studies h...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K47/69A61K41/00A61K31/704A61P35/00
CPCA61K47/64A61K47/6931A61K41/0052A61K31/704A61P35/00A61K2300/00
Inventor 顾忠伟吴花雨徐翔晖李亚超钟单张志军
Owner NANJING IND INST FOR ADVANCED INTELLIGENT EQUIP
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