Immune escape nano preparation, preparation method and application

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...

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

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