Targeted replication stress vulnerability anti-non-small cell lung cancer metastasis composition and application thereof

By designing dual-responsive polymer prodrugs to form amorphous phase nanomicelles, and utilizing the response of matrix metalloproteinases and acid-sensitive chemical bonds, the problem of uneven drug release was solved, achieving effective treatment and drug resistance inhibition of non-small cell lung cancer metastases.

CN122321164APending Publication Date: 2026-07-03南昌大学第一附属医院
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Patent Information

Application Number
CN202610638953.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-05-11
Publication Date
2026-07-03

AI Technical Summary

Technical Problem

In existing technologies, the active molecules of drugs for treating metastatic non-small cell lung cancer are released unevenly within the lesion tissue, leading to misalignment of the drug in time and space. This results in the inability to effectively block the replication stress repair pathway of tumor cells, thus inducing drug resistance.

Method used

The dual-responsive polymer prodrug is used to form amorphous phase nanomicelles by combining the block copolymer backbone, matrix metalloproteinase cleavage peptide sequences and active molecular groups. The response of matrix metalloproteinase and acid-sensitive chemical bonds ensures the synchronous release of replication stress inducers and ATR kinase inhibitors in the lesion microenvironment, blocking the DNA replication fork repair pathway.

Benefits of technology

It achieves simultaneous drug release in the lesion area, improves anti-tumor effect, reduces drug resistance, and enhances the treatment effect on non-small cell lung cancer metastases.

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Abstract

The invention relates to the field of biological medicine, and discloses a targeted replication stress vulnerability non-small cell lung cancer metastasis resistant composition and application thereof. The polymer prodrug is composed of a block copolymer main chain, a matrix metalloproteinase cleavage peptide sequence coupled to a hydrophilic end and an active molecule group coupled to a hydrophobic end based on an asymmetric graft structure, and the active molecule group is composed of a replication stress inducer and an ATR kinase inhibitor. Through the asymmetric grafting structure, the micelle core is maintained in an amorphous phase state, a permeation barrier generated by spontaneous crystallization of components is eliminated, the amorphous phase core provides a proton permeation channel, in-situ synchronous release of a multi-target drug is ensured, a DNA replication fork repair path is blocked, and a cell mitosis disaster is induced, so that the drug delivery efficiency is improved, and the drug delivery efficiency is improved. The spatial and temporal distribution coincidence of multi-drug intervention in a pathological target region is maintained, and the drug resistance risk is avoided.
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