Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof

A drug delivery system and multi-drug resistance technology, applied in the field of medicine, can solve problems such as insufficient drug accumulation, and achieve the effects of increasing retention, improving curative effect, and inhibiting the growth of multi-drug-resistant breast cancer.

Inactive Publication Date: 2016-08-31
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to overcome the problems of drug resistance of tumor cells, premature drug release of conventional polymer micelles, and insufficient drug concentration or drug accumulation at the tumor site, and provide a nano Drug delivery system and its preparation method and application

Method used

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  • Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof
  • Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof
  • Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Example 1: Preparation of monomeric tetrahedral tetraphenylmethane derivatives.

[0036] Schematic diagram of tetrahedral monomer molecule and CB[8] (see figure 1 ), where D 3 Molecule as an example to illustrate the preparation process of tetrahedral tetraphenylmethane derivatives, Com-1~6 are contained in figure 1 in the described structure. The synthesis process can refer to the literature Nat. Commun. 2014, 5 , 5574. Tetrakis(4-bromomethyl-phenyl)methane (30 mg, 0.043 mmol) and compound B30 (35.7 mg, 0.18 mmol) were weighed and dissolved in THF (2 mL) and acetonitrile (6 mL), heated to reflux for 24 After 1 hour, it was naturally cooled to room temperature. The solvent was removed by rotary evaporation, acetone (10 mL) was added, the precipitate was filtered and washed with acetone (10 mL), recrystallized with acetonitrile, filtered and dried to obtain a yellow powder (35.4 mg, 55%) 1 H NMR (400 MHz, DMSO): δ 9.19 (d, J = 5.3 Hz, 8H), 8.53 (d, J = 5.4...

Embodiment 2

[0037] Example 2: Preparation of SOF nanoparticle drug-loading system and characterization of its assembly mode.

[0038] According to the report of our previous research work ( Nat. Commun. 2014, 5 , 5574.) Tetrahedral molecules with arylpyridinium salt groups at the end groups can form ordered 3D supramolecular organic frameworks (SOFs) in aqueous solution, and the stoichiometric ratio of tetraphenylmethane derivatives to CB[8] molecules Mix 1:2 in water, heat and sonicate to disperse and dissolve the sample and cool to room temperature, that is, assemble in water to obtain the corresponding assembly. Through the Job plots experiment of observing the fluorescence spectrum, it was further confirmed that the phenylpyridinium cation unit of the target molecule was combined with CB[8] at a stoichiometric ratio of 2:1. reported by Isaacs et al. 1 H NMR competition assay method at 50 mM CD 3 CO 2 Na as D of buffer (pD = 4.74) 2 In O solution, we determined that the apparen...

Embodiment 3

[0039] Example 3: Characterization of the solution phase order of SOF nanoparticles.

[0040] Solution Phase Synchrotron Radiation Source (XRD) experiment: The X-ray diffraction data was tested by Shanghai Light Source (SSRF) Diffraction Line Station BL14B1, and the X-ray beam wavelength is 1.2398 Å. The BL14B1 line station monochromatizes the X-ray beam through a deflection magnet and a Si (111) double crystal monochromator. The focal diameter of the spot is 0.5 mm, the terminal is equipped with a Huber 5021 diffractometer, and the data is collected through a NaI scintillation detector. We characterized the order of SOF material nanoparticles by XRD experiments using synchrotron radiation sources, and confirmed that SOF nanoparticles have good order in the solution phase ( image 3 ). The carbon atoms in the center of the compound constitute the nodes of the network structure, and the ArPy groups of two adjacent molecules are included in the holes through CB[8], so that the...

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Abstract

The invention belongs to the field of pharmaceutical preparations and the technical field of breast cancers, and discloses a preparation method and application of a soluble nano drug delivery system inhibiting multidrug resistance breast cancer growth. According to the preparation method and application, water-soluble super-molecular organic framework (SOF) nano particles server as carriers for the first time, the system is obtained through self-assembly of tetrahedral molecules obtained through tetraphenylmethane derivatization and CB[8] in a water phase, and chemotherapy drugs such as neutral drug doxorubicin and anionic drug pemetrexed disodium, folate derivatives, targeted integrin specific ligands such as RDG peptide derivatives and infrared probe molecules such as IR-820 can be loaded simultaneously; the SOF nano-drug carrier has the release characteristic of pH dependence, is accumulated in tumor tissue at high concentration, has a specific growth inhibiting effect on tumor cells with drug resistance in the tumor tissue due to P-glycoprotein overexpression and can obviously increase the retention volume of a chemotherapy drug in multidrug resistance breast cancer tissue, effectively inhibit the multidrug resistance breast cancer growth and significantly improve the curative effect on a multidrug resistance breast cancer.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a nano drug delivery system capable of inhibiting the growth of multidrug-resistant breast cancer, a preparation method and application thereof. Background technique [0002] The death caused by cancer has always been one of the important causes of human death in the world today. Although scientists have conducted long-term and in-depth research on cancer treatment, the complete cure and elimination of cancer is still one of the biggest challenges facing mankind. As we all know, the high recurrence rate and treatment failure caused by chemotherapy-induced multidrug resistance (MDR, multidrug resistance) are important obstacles in the current clinical treatment of cancer. Scientists have proposed various possible mechanisms to explain the cause of MDR, including increasing drug efflux and promoting DNA repair by changing cell membrane transport proteins, or changing c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/48A61K31/519A61K31/704A61K47/16A61K49/00B82Y5/00A61P35/00A61K31/337
CPCA61K9/14A61K31/337A61K31/519A61K31/704A61K47/16A61K49/00B82Y5/00
Inventor 黎占亭田佳姚池张丹维
Owner FUDAN UNIV
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