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Bionic nano hydrogel coated with a macrophage membrane and loaded with manganese dioxide MnO2 and cis-platinum Pt as well as preparation and application thereof

A nano-hydrogel and biomimetic nano-technology, which is applied in animal cells, vertebrate cells, blood/immune system cells, etc., can solve the problems of early drug release of diagnostic reagents, low BBB efficiency, and limited drug loading, and achieve Enhance the effect of chemical kinetics and chemotherapy combination therapy, the preparation process is environmentally friendly, and the effect of high drug loading rate

Inactive Publication Date: 2021-11-02
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a biomimetic nano-hydrogel loaded with manganese dioxide MnO2 and cisplatin Pt coated with a macrophage cell membrane and its preparation and application, so as to overcome the low efficiency and low efficiency of the existing BBB crossing strategy. Defects such as limited drug loading, early drug release and single diagnostic reagents

Method used

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  • Bionic nano hydrogel coated with a macrophage membrane and loaded with manganese dioxide MnO2 and cis-platinum Pt as well as preparation and application thereof
  • Bionic nano hydrogel coated with a macrophage membrane and loaded with manganese dioxide MnO2 and cis-platinum Pt as well as preparation and application thereof
  • Bionic nano hydrogel coated with a macrophage membrane and loaded with manganese dioxide MnO2 and cis-platinum Pt as well as preparation and application thereof

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Experimental program
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Effect test

Embodiment 1

[0067] First, PVCL-COOH NGs were synthesized by precipitation polymerization: 469.5 mg of N-vinylcaprolactam (VCL, purchased from Sigma-Aldrich), 24.6 mg of N,N'-bisacryloylcystamine (BAC, purchased from Alfa (China) Chemical Co., Ltd.) and 7.9 mg of sodium dodecyl sulfonate (SDS, purchased from Sigma-Aldrich) were dissolved in 30 mL of deionized water, in N 2 Stir at 70°C for 30 min, then slowly add 1.25 mL of free radical initiator ACMA (17.5 mg, Japan Wako Pure Chemical Industry Co., Ltd.) dropwise to the above mixture with a syringe, react for 5 min, and then add 27 mg of acrylic acid mono body (AAc, purchased from Aladdin), and then at 70 ° C and N 2 The atmosphere continued to stir for 4h. After the reaction, dialyze for 3 days to remove unreacted monomer and surfactant. After the obtained PVCL-COOH NGs (210 mg) were activated by EDC / NHS (287.55 mg / 172.635 mg) for 2 hours, 200.4 μL of ethylenediamine (EDA) was added to react at room temperature for 3 days to obtain ami...

Embodiment 2

[0073] To the PVCL-COOH NGs, PVCL-NH that embodiment 1 prepares 2 NGs, M@P NGs, PM@P NGs and MPM@P NGs for characterization. The hydrodynamic particle size distribution and potential changes are as follows: figure 2 As shown in a and 2b, after PVCL-COOH NGs were modified by ethylenediamine, the hydrodynamic particle size decreased from 298.9±15.3nm to 278.9±3.9nm, and the potential changed from -13.7mV to 17.5mV, which proved that the surface carboxyl group was successfully transformed is a positively charged amino group (-NH 2 ). Loaded with MnO 2 After being combined with Pt, the hydrodynamic particle size increased to 301.5±3.1nm, and the potential changed from positive charge to negative charge (-10.2mV), indicating that MnO 2 and a successful load of Pt. After using the Avanti micro-extruder to coat the macrophage membrane, the hydrodynamic particle size was significantly reduced to 270±3.7nm, and the potential increased slightly (-6.1mV), indicating that the macrop...

Embodiment 3

[0078] The morphology and composition of the nanogels were studied by TEM and elemental energy dispersive spectroscopy. Such as image 3 a-b, TEM images of PM@P NGs and MPM@P NGs before and after coating macrophage membranes and corresponding element energy spectra. It can be seen from the figure that the PM@P NGs before coating is relatively loose, and the content of P element is relatively low; while the MPM@P NGs after coating becomes relatively compact due to repeated extrusion by the extruder, and the content of each element The distribution is relatively concentrated. Among them, the content of P element, which represents the phospholipid bilayer, was significantly increased, and a layer of macrophage cell membrane with a thickness of about 25nm was evenly coated on the outside, which fully proved that the cell membrane had successfully coated the surface of PM@P NGs.

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Abstract

The invention relates to a bionic nano hydrogel coated with a macrophage membrane and loaded with manganese dioxide MnO2 and cis-platinum Pt as well as preparation and application thereof. The bionic nano hydrogel is coated with the macrophage membrane; and the nano hydrogel is poly (N-vinyl caprolactam) (PVCL) nano hydrogel loaded with manganese dioxide (MnO2) and a chemotherapeutic drug cis-platinum. According to the prepared bionic drug-loaded nano hydrogel coated with the macrophage membrane, on one hand, through combined chemotherapy and enhanced chemokinetic therapy (CDT), the half inhibitory concentration (IC50) of the bionic drug-loaded nano hydrogel is remarkably reduced, and the drug safety index (Safety index) and the tumor cell apoptosis rate are increased; and moreover, the integrin [alpha]4 and [beta]1 on the surface of the macrophage membrane can effectively improve the proportion of the integrin [alpha]4 and [beta]1 penetrating through the blood brain barrier (BBB) to target brain glioma, and has a potential application prospect in the aspect of tumor in-situ tumor diagnosis and treatment.

Description

technical field [0001] The invention belongs to the field of functional bionic materials and their preparation and application, in particular to a macrophage membrane-coated biomimetic nano hydrogel loaded with manganese dioxide MnO2 and cisplatin Pt, and its preparation and application. Background technique [0002] Glioma is the most aggressive and lethal primary brain tumor of the central nervous system, with a poor prognosis and easy recurrence, with a five-year survival rate of less than 5% (Kui Wang, et al. Adv. Funct. Mater. 2020 , 2007166). At present, the main methods for the treatment of glioma are surgery, radiotherapy and chemotherapy. Although many efforts have been made in the treatment of glioma in recent years, due to the existence of the blood-brain barrier (BBB), the The drugs that can enter the intracranial tumor site are very limited, which greatly limits the effect of diagnosis and treatment of glioma. The BBB is mainly composed of brain endothelial ce...

Claims

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Application Information

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IPC IPC(8): A61K49/08A61K49/12A61K9/51A61K9/06A61K33/243A61K45/00A61K47/32A61K47/46A61K49/18A61P35/00C12N5/0786A61K33/32
CPCA61K33/243A61K33/32A61K45/00A61K9/5192A61K9/5176A61K9/06A61K47/32A61P35/00C12N5/0645A61K49/126A61K49/1824A61K49/1803A61K49/08A61K2300/00
Inventor 史向阳肖婷婷徐放
Owner DONGHUA UNIV
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