Preparation method and application of liposome vesicle-encapsulated targeted protein degradation nanoparticles

Targeted protein degradation nanoparticles encapsulated in liposome vesicles solve the off-target and hook effect problems of protein degradation targeting chimeras, achieve efficient targeting and long circulation in tumor cells, and provide a precise platform for protein degradation.

CN119367299BActive Publication Date: 2025-09-30UNIV OF SCI & TECH OF CHINA
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Patent Information

Application Number
CN202411574852.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-11-06
Publication Date
2025-09-30
Estimated Expiration
2044-11-06

AI Technical Summary

Technical Problem

Protein degradation targeting chimeras have high off-target potential, limited hook effect, and poor pharmacokinetics in tumor cells, which restrict their application and efficacy in vivo.

Method used

Targeted protein degradation nanoparticles encapsulated in liposome vesicles are prepared by combining hyaluronic acid and liposome vesicles to form negatively charged nanoparticles, thereby targeting multiple target proteins and avoiding unstable diffusion in the blood circulation.

Benefits of technology

It improves the in vivo utilization of protein degradation-targeted chimeras, increases targeted accumulation in tumor cells, achieves efficient protein degradation effects and long circulation time, and provides a precise protein degradation platform.

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Abstract

The present invention discloses a method for preparing liposome-encapsulated targeted protein degradation nanoparticles and their application. The present invention blends a polymetformin-based protein degradation targeted chimera with hyaluronic acid to form polyprotein degradation targeted chimera nanoparticles through electrostatic adsorption. The liposome vesicles are then blended with the polyprotein degradation targeted chimera nanoparticles and co-extruded to obtain liposome-encapsulated targeted protein degradation nanoparticles. The liposome-encapsulated targeted protein degradation nanoparticles designed by the present invention can overcome the hook effect of the protein degradation targeted chimera in tumor cells and achieve long-term circulation of the protein degradation targeted chimera in the body, thereby maximizing the in vivo utilization of the protein degradation targeted chimera and enhancing the anti-tumor effect.
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