Nano vesicle jointly loaded with PD-L1 antibody and STING agonist as well as preparation method and application thereof

Abstract

The invention provides a PD-L1 antibody and a STING agonist loaded nano-vesicle, the structure of the nano-vesicle comprises a shell and an inner core, the shell is prepared from a lipid bilayer membrane, the shell is coupled with an MMP-2 sensitive polypeptide chain, the polypeptide chain is coupled with a PD-L1 antibody, and the shell is also coupled with PEG; and the inner core of the gene is an STING agonist. According to the nano-vesicle disclosed by the invention, the long-chain PEG is used as a protective barrier of an antibody, so that non-specific binding of a PD-L1 antigen on normal tissues of the PD-L1 antibody is prevented; the nano-vesicle has the pH and MMP-2 dual sensitivity, and the shell liposome is coupled with the MMP-2 sensitive peptide chain, such that the vesicle can responsively release the PEG layer and the PD-L1 antibody when the vesicle reaches the acidic and high MMP-2 concentration residual tumor micro-environment, and the surface charge of the vesicle is converted from negative to positive after the release so as to effectively promote the endocytosis of the STING activator carrier by the antigen-presenting cells.

Description

technical field [0001] The invention belongs to the technical field of tumor diagnosis and treatment, and in particular relates to a nanovesicle jointly loaded with PD-L1 antibody and STING agonist, its preparation method and application. Background technique [0002] STING activators can effectively inhibit tumor growth, but STING activation can induce PD-L1 upregulation and immune escape, thereby limiting its efficacy, and the curative effect of STING activators and PD-L1 antibody synergistic therapy is significantly better than single drug therapy. The STING activating drugs currently on the market are all hydrophilic small molecule drugs, which are easy to degrade and difficult to enter cells, and are limited to intratumoral injection therapy, and are not suitable for cancer treatment that cannot be directly injected. At present, many studies have designed different carriers to load STING activators for anti-tumor therapy. [0003] Existing studies have reported that th...

AI Technical Summary

Problems solved by technology

In addition, the action sites of STING agonists and αPD-L1 are located on the intracellular and extracellular membranes, respectively, which makes it difficult to control their proportion and distribution in the tumor site after administration separately, which may affect the effect of synergistic therapy

And free PD-L1 antibody treatment can non-specifically bind to normal tissues expressing PD-L1, thus causing immune-related toxic side effects

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