PH-sensitive liposome as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biological medicines, in particular to a pH-sensitive liposome as well as a preparation method and application thereof. The pH-sensitive liposome is prepared from the following medicines and a liposome carrier according to the following amount of substance: (2, 3-dioleoyl-propyl)-trimethyl ammonium-chloride salt, dioleoyl phosphatidylcholine, cholesterol succinic acid monoester and DSPE-PEGn-pep in a molar ratio of (2 to 5): (0.5 to 1.5): (0.5 to 1.5): (0.1 to 0.3), the total mass ratio of the ICD inducer to the (2, 3-dioleoyl-propyl)-trimethyl ammonium-chloride salt, the dioleoyl phosphatidylcholine and the cholesterol succinic acid monoester is (5-12): 100; the mass ratio of the adenosine pathway blocking agent to the ICD inducer is (0.5-2): (0.5-3). The ICD inducer and the adenosine pathway inhibitor are combined for use, so that the problems that the anti-tumor curative effect is poor and tumor immunity escapes when only the ICD inducer is used for treatment are solved, and in-vivo co-delivery of the ICD inducer and the adenosine pathway inhibitor is realized by utilizing the liposome carrier; the pH sensitive characteristic of the POL effectively ensures that the POL is kept stable in the blood circulation process.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a pH-sensitive liposome and its preparation method and application. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Chemotherapy is one of the most classic cancer treatment methods, for example, the use of cytotoxic drugs such as anthracyclines, such as oxaliplatin, mitoxantrone, doxorubicin, cyclophosphamide, etc., can induce tumor cell immunity Induced cell death (ICD) to enhance anti-tumor immunity. Adenosine triphosphate (ATP) generated during this process can recruit DCs, thereby activating the maturation and infiltration of T cells and memory T cells into tumors, tr...

AI Technical Summary

Problems solved by technology

Unfortunately, the response rate among patients who rely solely on ICD-inducing agents is still low, and the clinical effect is unsatisfactory

The main reason is that the immune-stimulating ATP produced after ICD induction will be rapidly degraded into immunosuppressive adenosine by the highly expressed CD39 and CD73 in the tumor microenvironment, and adenosine interacts with G protein-coupled adenosine receptors expressed on immune cells or tumor cells. A2a (A2aR) binding, leading to immune escape and malignancy progression

The problem of poor anti-tumor efficacy and immune evasion of tumors that only use ICD inducers needs to be improved and resolved

Images