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Immune escape nano preparation, preparation method and application

A nano-preparation and immune escape technology, applied in the field of biomedicine, can solve the problems of complex process, high cost, loss of immune monitoring, etc., and achieve the effect of improving the targeting effect

Pending Publication Date: 2022-03-25
ANHUI MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current design of nano-preparations based on the CD47 pathway has the following problems: (1) In addition to binding to the signal regulatory protein SIRPα on phagocytes, CD47 also binds to a variety of extracellular proteins such as integrins, thrombosis protein 1 (TSP1), etc. role, and participate in the regulation of a variety of signaling pathways, using CD47 to achieve immune escape will also affect related signal transduction and bring adverse effects (KaleA, Rogers NM, Ghimire K. Thrombospondin-1CD47 Signaling: From Mechanisms to Medicine. Int J Mol Sci.2021; 22(8):4062; Logtenberg MEW, Scheeren FA, SchumacherTN. The CD47-SIRPa Immune Checkpoint. Immunity.2020; 52(5):742-752.); (2) some cancers were found in the experiment subtypes developed resistance to this treatment (Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, et al. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy.NatImmunol.2018; 19(1):76-84.), in some solid tumors, tumor-associated macrophages constitute 50% of the plastic and heterogeneous cell population of the tumor microenvironment (TME) (Vitale I , Manic G, Coussens LM, etal.Macrophages and Metabolism in the Tumor Microenvironment.Cell Metab.2019; 30(1):36-50.), and tumor-associated macrophages also express CD47 receptor SIRPa, based on CD47 nanoparticles It will be recognized by tumor-associated macrophages and not taken up (Gautam PK, Acharya A. Suppressed Expression of Homotypic Multinucleation, Extracellular Domains of CD172a(SIRP-a) and CD47(IAP) Receptors in TAMs UpRegulated by Hsp70–Peptide Complex in Dalton' sLym phoma. Scand J Immunol, 2014; 80(1):22-35.)
[0005] In 2018, a study reported the second "don't eat me" signal (Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, et al. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy.Nat Immunol.2018;19(1):76-84.), that is, β2 microglobulin (β2M), β2M is the major histocompatibility complex (MHC)-I class highly expressed by tumor cells The light chain of the molecule sends a "don't eat me" signal by binding to the macrophage-expressed receptor LILRB1, resulting in a loss of immune surveillance
However, whether the application of β2M on nanocarriers will produce anti-phagocytic effects similar to those of CD47 has not been reported, and if β2 microglobulin is used as nanocarriers, the process is complicated and the cost is high

Method used

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  • Immune escape nano preparation, preparation method and application
  • Immune escape nano preparation, preparation method and application
  • Immune escape nano preparation, preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0030] The preparation of embodiment 1 nanomicelle MSP-PEG-PCL

[0031] The preparation method of nanomicelle MSP-PEG-PCL:

[0032] (1) Weigh 20 mg of Mal-PEG2000-PCL 2000 and dissolve it in 2 ml of DMSO, then drop it into PBS buffer solution with pH 7.4, stir well and then dialyze overnight to obtain a micellar solution;

[0033] (2) The amino acid sequence of the polypeptide MSP is: Cys-GPLGVRGTLSQPKIVKWDRDM, according to the sequence of solid-phase synthesis of the polypeptide MSP, take 11 mg of the polypeptide MSP, add it to the micellar solution in step (1), stir and react at room temperature for 24 hours, and then transfer the reaction solution to Dialysis bags (MWCO3500Da), and dialyzed with deionized water for 24 hours to remove unreacted polypeptides to obtain nanomicelle MSP-PEG-PCL.

[0034] figure 1 is the proton nuclear magnetic resonance spectrum of Mal-PEG-PCL, figure 2 is the proton nuclear magnetic resonance spectrum of the polypeptide MSP, image 3 For t...

Embodiment 2

[0036] Adopt photosensitizer Ce6 as antitumor drug, entrapped in the nano-micelle MSP-PEG-PCL that embodiment 1 makes, method is as follows: the nano-micelle MSP-PEG-PCL that embodiment 1 makes is lyophilized, takes 10mg and 0.5mg photosensitizer Ce6 were dissolved in 0.5mL solvent DMSO to obtain a mixed solution, which was added to 3mL deionized water, stirred for 1 hour, then ultrasonicated for 5 minutes in an ice-bath probe, and finally transferred to a dialysis bag (MWCO 3500Da) Dialyzed with deionized water to obtain immune escape nano preparations.

[0037] The transmission electron microscope picture of the immune escape nano-preparation that embodiment 2 makes is shown in Figure 4 ,Depend on Figure 4 It can be seen that the appearance of the Ce6-loaded immune escape nano-preparation is a spherical structure with a smooth and complete surface.

Embodiment 3

[0039] Adopt photosensitizer Ce6 as antitumor drug, be loaded in the nanomicelle MSP-PEG-PCL that embodiment 1 makes, method is as follows: After the nanomicelle MSP-PEG-PCL that embodiment 1 makes is lyophilized, take Dissolve 10mg and 0.8mg of photosensitizer Ce6 in 0.5mL solvent DMSO to obtain a mixed solution, add the mixed solution to 3mL deionized water, stir for 1h, then ultrasonicate the probe for 5min in an ice bath, transfer to a dialysis bag (MWCO 3500Da) for use Dialyzed with deionized water to obtain immune escape nano-preparation.

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Abstract

The invention relates to an immune escape nano preparation, and belongs to the technical field of biological medicines. The immune escape nano-preparation comprises a nano-micelle and an antitumor drug entrapped in the nano-micelle, the nano-micelle is formed by connecting polypeptide MSP and a micelle material Mal-PEG-PCL, the polypeptide MSP is designed based on a crystal structure in which beta 2M and LILRB1 interact, the amino acid sequence of the polypeptide MSP is Cys-GPLGVRGTLSQPKIVKWDRDM, and after the polypeptide MSP is coupled with Mal-PEG-PCL, the polypeptide MSP and the micelle material Mal-PEG-PCL are coupled to form the nano-micelle. The nano-micelle capable of actively escaping macrophage phagocytosis can be formed, an anti-tumor drug is entrapped in the nano-micelle to obtain the immune escape nano-preparation, and the nano-preparation can actively escape macrophage phagocytosis and can be taken by tumor-related macrophages.

Description

technical field [0001] The invention relates to an immune escape nano preparation, a preparation method and an application, and belongs to the technical field of biomedicine. Background technique [0002] In recent years, nanoparticle-based drug delivery platforms have become important vehicles to overcome the pharmacokinetic limitations of traditional drug formulations. Rationally designed nano-preparations have the advantages of good circulation time, targeting and biocompatibility. For example, the marketed nano-preparation doxorubicin liposome has a good long-term circulation effect in the body, and compared with patients receiving conventional preparations, the use of doxorubicin liposome reduces cardiotoxicity. Another nano-preparation - paclitaxel micelles, has also been approved for clinical treatment of tumors. [0003] The clinical application of nano-delivery platforms (such as nano-preparations of doxorubicin and paclitaxel) has improved the drug safety of pati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/64A61K47/65A61K45/00A61P35/00B82Y5/00B82Y40/00
CPCA61K47/64A61K47/6907A61K47/65A61K45/00B82Y5/00B82Y40/00A61P35/00
Inventor 汤继辉邹千里鲍健威
Owner ANHUI MEDICAL UNIV
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