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Sphere-in-sphere nanoparticle and preparation method thereof

A nanoparticle and spherical technology, which is applied in the field of spherical nanoparticles and its preparation, can solve the problems of complex preparation process, low drug loading, poor drug safety, etc.

Active Publication Date: 2021-10-22
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Based on this, it is necessary to address the problems of poor drug safety, low drug loading, and complicated preparation process of traditional nanocarrier drugs, and provide a ball-in-ball spherical nanoparticle and its preparation method

Method used

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  • Sphere-in-sphere nanoparticle and preparation method thereof
  • Sphere-in-sphere nanoparticle and preparation method thereof
  • Sphere-in-sphere nanoparticle and preparation method thereof

Examples

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preparation example Construction

[0035]The invention relates to an environment-responsive "ball-in-a-ball" nanoparticle and its preparation method and application. The nanoparticle is a "ball-in-ball" nanoparticle prepared by self-assembly of two amphiphilic monomer molecules with different lengths as the unit. Two kinds of amphiphilic monomer molecules, the first monomer molecule includes a first hydrophobic molecule and a hydrophilic anti-tumor drug connected to each other, and the second monomer molecule includes a second hydrophobic molecule connected in sequence, an environment-responsive link Molecules, hydrophilic immunomodulatory adjuvant molecules. When the ball-in-a-ball nanoparticle reaches the local tumor, the environment-responsive linker molecules are broken in response to the microenvironmental conditions, and the external hydrophilic immunomodulatory adjuvant molecules and the internal spherical anti-tumor drugs (chemotherapy drugs / photosensitive drugs, etc.) A sphere is disintegrated and rel...

Embodiment

[0071] S1: Addition of N-hydroxysuccinimidyl 3-(2-pyridyldimercapto)propionate and dithiothreose to the hydrophobic molecule 1,2-dioleoyl-SN-glycero-3-phosphoethanolamine Alcohols are modified with sulfhydryl groups, the mass ratio of the three is (5.2-10.4) mg: (3-6) mg: (3.9-7.8) mg, and the reaction is stirred at room temperature for 12-24 hours;

[0072]S2: Add 3-(2-pyridyldimercapto) N-hydroxysuccinimide propionate to the hydrophilic drug molecule doxorubicin hydrochloride for pyridyl dithiol modification, the doxorubicin hydrochloride and 3-( The mass ratio of N-hydroxysuccinimide 2-pyridyldimercapto) propionate is (4.0-8.0) mg: (3.0-6.0) mg, and the reaction is stirred at room temperature for 8-16 hours;

[0073] S3: Mix the substances obtained in the above S1 and S2, stir and react at room temperature for 24-48 hours, then dialyze and freeze-dry;

[0074] S4: Mix the environment-responsive linker molecule MMP-9 polypeptide (sequence: NH2-ESWTKKSPSPEFSGMGPQGIAGQR-COOH)...

experiment example

[0080] 1. Cellular uptake experiment of matrix metalloenzyme 9 (MMP-9)-responsive "ball-in-ball" nanoparticles:

[0081] In order to observe the uptake of tumor cells to MMP-9 environment-responsive "ball-in-ball" nanoparticles, E.G7-OVA tumor cells were placed in a confocal dish, and the tumor cells were co-incubated with nanoparticles for 2 hours (according to the Mycin 2μM was used to calculate the dosage), washed with PBS, and fixed with fixative solution, and the distribution of MMP-9 environment-responsive "ball-in-ball" nanoparticles in tumor cells was observed by laser confocal microscope (Leica, TCS SP5) , Operate in dark all the way. The monomer molecule A of the same concentration was used as a control, and the monomer molecule A was the product obtained in S3. Such as Figure 4 It was shown that MMP-9 environment-responsive "ball-in-ball" nanoparticles enhanced the uptake of chemotherapeutic drugs by tumor cells compared to chemotherapeutic drug molecules alone. ...

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Abstract

The invention discloses a sphere-in-sphere nanoparticle which is of a spherical structure obtained by self-assembly of a first monomer molecule and a second monomer molecule, the first monomer molecule comprises a first hydrophobic molecule and a hydrophilic anti-tumor drug which are connected with each other, and the hydrophilic anti-tumor drug is used for causing death of tumor cells; and the second monomer molecule comprises a second hydrophobic molecule, an environment-responsive connecting molecule and a hydrophilic immunoregulation adjuvant molecule which are connected in sequence, the first monomer molecule and the second monomer molecule are distributed alternately, the first monomer molecule forms a first sphere, the second monomer molecule forms a second sphere, the sphere centers of the first sphere and the second sphere coincide, the outer diameter of the second sphere is larger than that of the first sphere, first hydrophobic adjuvant molecules are distributed on the inner side of the first sphere, and second hydrophobic adjuvant molecules are distributed on the inner side of the second sphere. The invention further discloses a preparation method of the sphere-in-sphere nanoparticle.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to ball-in-spherical nanoparticles and a preparation method thereof. Background technique [0002] The development of nano-drug preparations or nano-drug carriers has become a hot spot in the field of international medicine. Nanomedicine can not only improve the stability and release performance of drugs, increase the bioavailability of drugs, but also improve the targeting of drugs and realize the co-delivery of multi-component functional molecules, which has unique advantages in the combination therapy of tumors. [0003] However, at present, nanocarriers are mostly prepared from nanomedical materials. Nanocarrier particles are small in size, large in specific surface area, rich in surface states, and high in chemical activity. They have many special properties that are not found in bulk and ordinary powders. Materials may cause cell death, morphological changes, and chromosome...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/24A61K31/704A61K39/39A61K41/00A61K47/54A61K47/65A61P35/00
CPCA61K9/5123A61K47/65A61K47/548A61K39/39A61K31/704A61K41/0057A61P35/00A61K2039/55561A61K2300/00
Inventor 刘兰霞邓博冷希岗马兵
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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