Functional nucleic acid of skeleton integrated nucleoside analog medicine as well as derivative and application thereof

Abstract

The invention belongs to the technical field of biological medicine and particularly discloses functional nucleic acid of a skeleton integrated nucleoside analog medicine and a derivative thereof as well as a preparation method thereof, wherein the derivative is obtained by conjugating or self-assembling the functional nucleic acid of the skeleton integrated nucleoside analog medicine and one of apolymer, a hydrophobic molecule and a transfection agent. Compared with the prior art, the functional nucleic acid of the skeleton integrated nucleoside analog medicine and the derivative thereof canefficiently enter cells and perform the gene regulating and control function by utilizing the functional nucleic acid of the skeleton integrated nucleoside analog medicine; the functional nucleic acid of the skeleton integrated nucleoside analog medicine can be degraded by nuclease and release active components of the nucleoside analog medicine, so the chemical treatment effect is achieved. Therefore, the functional nucleic acid of the skeleton integrated nucleoside analog medicine and the derivative thereof can realize combined treatment of gene treatment and chemical treatment simply and efficiently and avoid the complex synthesis step.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to functional nucleic acids and derivatives of backbone-integrated nucleoside analog drugs, their preparation methods and applications. Background technique [0002] During chemotherapy, tumor cell drug resistance is a huge challenge in the field of cancer treatment today (Nat. Rev. Cancer 2013, 13, 714-726.). [0003] There are many reasons for drug resistance of tumor cells, such as enhanced anti-apoptotic ability, increased drug pumping rate, etc. (Nat. Rev. Cancer 2012, 12, 494-501.). For example, in order to avoid the damage of chemotherapy drugs, tumor cells overexpress anti-apoptotic proteins during chemotherapy, thereby inhibiting the anti-tumor activity of chemotherapy drugs. In addition, tumor cells can also upregulate the expression of drug transporters, which have the ability to pump chemotherapy drugs out of the cell, so upregulation of transporters wil...

AI Technical Summary

Problems solved by technology

[0008] (1) The hydrophilicity and hydrophobicity of gene drugs and chemotherapeutic drugs are often quite different, so it is difficult to design an ideal nanocarrier to efficiently entrap two substances at the same time;

[0009] (2) It is difficult to accurately control the loading amount and ratio of gene drugs and chemotherapy drugs in the carrier;

[0010] (3) The release time sequence of gene drugs and chemotherapy drugs is difficult to precisely control

[0011] The above difficulties will limit the application of gene-chemotherapy combination therapy in the treatment of drug-resistant tumors

Images