Fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as synthesizing method and application thereof

Abstract

The invention provides a fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as a synthesizing method and application thereof. The method comprises the following steps: performing cystamine modification on terminated methoxy polyethylene glycol; initiating a ring-opening polymerization of gamma-benzyl ester-L-glutamate-N-carboxyanhydride by utilizing the terminated amine of the terminated methoxy polyethylene glycol; connecting the product in the ring-opening polymerization and polyethyleneimine by utilizing 2,2'-dithio-diethyl isocyanate by virtue of an addition reaction to obtain the target product. According to the method, the synthesized copolymer is amphipathic, can be self-assembled to form nano-particles; chemotherapeutic medicines and genetic medicines can be simultaneously loaded to the copolymer when the copolymer is used as a medical vector; the copolymer can be completely dissociated and disintegrated by responding glutathione and other reductive substances, so that the vector can escape from endosome to cytoplasm, medicines can be quickly released, and the treatment effect can be improved. The method can be used for controlling the molecular weight and length of each fragment in the segmented copolymer, is mild in reaction condition, and is suitable for more medicine types.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a completely dissociable polyethylene glycol-poly(L-glutamic acid-γ-benzyl ester)-polyethyleneimine copolymer and its synthesis method and application. Background technique [0002] Malignant tumor is one of the main threats to human health, and its treatment is a worldwide problem. Chemotherapy, like surgery and radiotherapy, is currently the mainstay of cancer treatment. Chemotherapy is a method that uses cytotoxic drugs to kill tumor cells for therapeutic purposes. However, cytotoxic drugs, such as doxorubicin, paclitaxel, epirubicin, and docetaxel, are usually poorly water-soluble and non-selective, with low bioavailability, which can cause serious side effects. Moreover, tumor cells are prone to multidrug resistance during chemotherapy, and the curative effect is not ideal. According to the American Cancer Society estimates, more than 90% of cancer patients...

AI Technical Summary

Problems solved by technology

However, these imine bonds cannot guarantee the stability of the gene carrier, and may have been dissociated before reaching the tumor tissue and entering the cells, making it difficult to guarantee the transfection effect

[0004] Sequential combination therapy is often used in clinical malignant tumors to overcome the unsatisfactory therapeutic effect of single agents

However, this combination therapy cannot achieve combination at the microscopic level, and requires repeated medications, which brings unnecessary troubles to patients.

At the same time, this combined treatment method is difficult to ensure the combined drug at the same site, the effect of synergistic anti-tumor treatment is not easy to reflect, and the clinical efficacy is not satisfactory.

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