Biodegradable anti-tumor bonding prodrug with temperature sensitivity and preparation method thereof

Abstract

The invention discloses a biodegradable anti-tumor bonding prodrug with temperature sensitivity and a preparation method of the biodegradable anti-tumor bonding prodrug. The anti-tumor bonding prodrug comprises a polyethylene glycol and polylactide amphiphilic block main chain, and oligomeric polyethylene glycol, drug molecules and temperature-sensitive functional groups are grafted on the main chain by means of a thiol-ene click reaction, a condensation reaction, an esterification reaction, an azide-alkyne cycloaddition reaction and the like. The anti-tumor bonded prodrug is good in biocompatibility and easy to degrade, has the characteristics of realizing hydrophilic and hydrophobic conversion through thermo-sensitive stimulation response, releasing drugs through pH stimulation response and the like, can improve the aggregation capability of micelle drugs in tumor tissues and the permeability of the micelle drugs to the tumor tissues, realizes accurate targeted release of the drugs, and has a good application prospect. The treatment effect and utilization rate of the medicine are improved; the preparation method of the anti-tumor bonding prodrug has the advantages of simple operation, mild conditions and few side reactions, and can be used for large-scale production.

Description

technical field [0001] The invention relates to an anti-tumor bonded prodrug, in particular to a biodegradable and temperature-sensitive anti-tumor bonded prodrug and a preparation method thereof, belonging to the field of biomedical materials. Background technique [0002] As one of the largest public health problems in the world, malignant tumors are the most persistent disease that threatens human health. At present, chemotherapy is the basic method for clinical treatment of malignant tumors, and it is also a systemic treatment method, which enters the blood circulation through oral, intravenous and body cavity administration. Tumor drugs have defects such as low water solubility, lack of selectivity, short half-life in vivo, and low drug utilization. Various deficiencies have greatly restricted the clinical application of traditional small molecule anti-tumor drugs, and it is difficult to give full play to their therapeutic effects. At present, the use of polymer prodru...

AI Technical Summary

Problems solved by technology

However, most of the micellar drug delivery systems reported so far have high synthesis conditions, complex steps, lack of certain biocompatibility and degradability of the carrier, and cannot simultaneously take into account the circulation stability in vivo and the uptake rate of tumor cells and tumor cells. Tissue accumulation ability, because the reason why micelles can maintain high stability in vivo is due to the protective effect of its hydrophilic shell, while the surface of tumor cells is a layer of hydrophobic oil layer, which will cause the interaction between micelles and tumor cell surface Rejection is not conducive to the entry of drug-loaded micelles into tumor cells, which in turn leads to low drug uptake by tumor cells; and the traditional micellar drug delivery system cannot rapidly release drugs at the tumor site only by passive targeted release of the EPR effect. These problems will make the human body’s utilization rate of tumor drugs low, reduce the therapeutic efficacy of drugs, and easily cause drug resistance in tumor cells sensitive to anti-tumor drugs. In general, simple micellar drug carriers can no longer meet the treatment requirements. According to the differences in the drug delivery process and the microenvironment inside and outside tumor cells, constructing an ideal micellar drug delivery system has become an urgent problem and research hotspot for researchers.

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