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Cell membrane coated nano bait for removing proinflammatory factors and inhibiting T cell activation as well as preparation method and application of cell membrane coated nano bait

A cell membrane and nanotechnology, applied in the field of biomaterials and medicine, can solve the problems of high cost, insufficient prevention, poor hydrolytic stability, etc., to achieve high safety, high neutralization efficiency of pro-inflammatory factors, and avoid adverse reactions.

Active Publication Date: 2022-05-13
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these protein drugs are often challenged by immunogenicity, poor hydrolytic stability, high cost, and antibody resistance after repeated dosing
Moreover, this single-target approach is often insufficient to halt or reverse the progression of autoimmune diseases involving complex genetic backgrounds and the involvement of multiple pro-inflammatory factors

Method used

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  • Cell membrane coated nano bait for removing proinflammatory factors and inhibiting T cell activation as well as preparation method and application of cell membrane coated nano bait
  • Cell membrane coated nano bait for removing proinflammatory factors and inhibiting T cell activation as well as preparation method and application of cell membrane coated nano bait
  • Cell membrane coated nano bait for removing proinflammatory factors and inhibiting T cell activation as well as preparation method and application of cell membrane coated nano bait

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0089] The preparation method of nano-bait

[0090] The application also provides a method for preparing the nanobait of the application, the method comprising:

[0091] (A) providing nanocores;

[0092] (B) Cell membranes of macrophages providing PD-L1 expression;

[0093] (C) wrapping the cell membrane on the nano-core to form the nano-bait.

[0094] The nano-cores of the present application can be prepared from raw materials by various methods known in the art (such as using nano-precipitation method), and can also be purchased directly from various suppliers. The nano-core can have an opposite potential to the cell membrane to form a charge attraction to further stabilize the nano-bait.

[0095] Macrophage cell membranes can be obtained by cell lysis and separation, for example, the lysis includes: ultrasonic lysis, enzymatic lysis, chemical lysis, homogenate lysis and / or hypotonic swelling lysis; the separation includes: centrifugation (for example, stepwise centrifuga...

Embodiment

[0122] The present application will be further elaborated below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. Those skilled in the art can make appropriate modifications and changes to this application, and these modifications and changes are all within the scope of this application.

[0123] For the experimental methods that do not indicate specific conditions in the following examples, conventional methods in the art can be used, for example, with reference to "Molecular Cloning Experiment Guide" (third edition, New York, Cold Spring Harbor Laboratory Press, New York: Cold Spring Harbor Laboratory Press, 1989), "Animal Cell Culture" (Animal Cell Culture, edited by R.I. Freshney, 1987) or according to the conditions suggested by the supplier. The DNA sequencing method is a routine method in the art, and commercial com...

Embodiment 1

[0126] Embodiment 1, preparation and characterization of PRM NDs nanobait

[0127] according to figure 1 The process described in A prepares the cell membrane-coated nanocomposite-PRM NDs nanobait of this application. Concrete preparation steps are as follows:

[0128] (1) Preparation of membrane material: mouse monocyte / macrophage-like cells RAW 264.7 (purchased from the Cell Bank of the Chinese Academy of Sciences, catalog number SCSP-5036, the medium is DMEM containing 10% FBS, 37 ° C, 5% CO 2 ) stimulated by IFN-γ (50ng / mL) for 48 hours and then suspended in a solution containing 20mM Tris·HCl (pH 7.5), 10mM KCl, 75mM sucrose, 2mM MgCl 2 and protease / phosphatase inhibitors (purchased from Pierce, Cat. No. A32953, each tablet dissolved in 10 mL of solution) in homogenization buffer. The cells in the suspension were disrupted with a JY92-IIN homogenizer (75W), and then the supernatant was collected by centrifugation at 20000g for 25 minutes, and the cell membrane was col...

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Abstract

The invention provides a cell membrane coated nano bait for removing proinflammatory factors and inhibiting T cell activation as well as a preparation method and application of the cell membrane coated nano bait. Specifically, the invention provides a nano bait, which comprises a nano core and a macrophage cell membrane which coats the nano core and is expressed by a programmed death ligand 1 (PD-L1). The nano bait can be PRM NDs, PRM is a PD-L1 expressed macrophage cell membrane, and PLGA is a nano core. The nano bait is applied to treatment of autoimmune diseases with high expression of proinflammatory factors and over-activation of T cells. The nano bait can effectively remove high-expression proinflammatory factors in rheumatoid arthritis and inflammatory bowel diseases, can inhibit excessive activation of T cells, has long-time blood circulation after systemic administration, and has great potential in clinical treatment of rheumatoid arthritis and inflammatory bowel diseases.

Description

technical field [0001] The invention belongs to the field of biomaterials and medical technology, in particular to a cell membrane-coated nano-bait for removing pro-inflammatory factors and inhibiting T cell activation, and a preparation method and application thereof. Background technique [0002] The destruction of immune tolerance to self-antigens represented by the continuous activation of T cells is the root cause of autoimmune diseases. Subsequent dysregulated inflammatory responses lead to the progression of autoimmune diseases, resulting in autoimmune damage to systemic organs. The activation of T cells is mediated by co-stimulatory signaling molecules, and programmed death receptor-1 (PD-1) is an important co-stimulatory signaling molecule that provides inhibitory signals to the activation of T cells. Under normal physiological conditions, programmed death ligand 1 (PD-L1) expressed in tissues binds to membrane-bound PD-1 (mPD-1) on T cells and transmits inhibitory...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/46A61K47/34A61K47/36A61K47/42A61K47/32A61K47/04A61K47/02A61P29/00A61P37/02A61P19/02A61P1/00A61P3/10B82Y5/00B82Y40/00
CPCA61K47/46A61K47/34A61K47/36A61K47/42A61K47/32A61K47/02A61P29/00A61P37/02A61P19/02A61P1/00A61P3/10B82Y5/00B82Y40/00
Inventor 殷黎晨侯梦滢
Owner SUZHOU UNIV
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