Medicine aptamer constructed by nucleoside analogue medicine molecules and preparation method and application thereof

Abstract

The invention discloses a medicine aptamer constructed by nucleoside analogue medicine molecules, a preparation method and application thereof. Structure units similar to the structures in the traditional aptamer sequence can be respectively replaced by utilizing nucleoside analogue medicine molecules with different structures through the medicine aptamer, thereby obtaining a medicine-containing oligonucleotide sequence with similar targeting functions. A series of medicine aptamers targeting to different tumors can be prepared by selecting aptamer sequences with different targeting receptors,and a universal novel precise targeted medicine is constructed for treating different types of tumors. The preparation method comprises the following steps of converting the nucleoside analogue medicine molecules with structures similar to the basic structural unit of nucleotide into the corresponding phosphoramidite monomers, and synthesizing a series of medicine aptamers with precise compositions and different sequences by utilizing solid-phase synthesis technology. The medicine aptamer disclosed by the invention has an original targeting function corresponding to the aptamer, thereby realizing specific targeting of different tumors, reaching a good medicine delivery effect and greatly improving therapeutic effect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a drug aptamer constructed from nucleoside analog drug molecules and its preparation method and application. Background technique [0002] Malignant tumor is one of the major diseases affecting human survival and health. At present, chemotherapy is one of the effective methods for the treatment of malignant tumors. However, in clinical treatment, due to the disadvantages of poor water solubility, non-targeting, long cycle time, low bioavailability, and large side effects (Nat. Rev. Cancer 2006, 6, 789.) of most chemotherapeutic drugs, patients It has endured great pain and brought certain limitations to its clinical application. [0003] With the development of nanotechnology, in the past few decades, scientists have reported a series of organic and inorganic nanoparticles, such as micelles, vesicles, liposomes, albumin nanoparticles, mesoporous inorganic materi...

AI Technical Summary

Problems solved by technology

However, the above method still has certain defects: 1) aptamer itself has no anticancer activity, and can only provide targeting function for drug molecules. side effect

2) Most aptamer-drug conjugates require additional chemical modification-responsive linkages to conjugate drugs and aptamers, making chemical synthesis and modification difficult

3) In practical applications, the chemical stability of aptamer is relatively poor, and it will be quickly recognized and degraded by nucleases in the blood after entering the blood, and its half-life in the blood is even only a few minutes

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