Preparation method of oxidoreduction responsiveness tumor-targeted cis-platinum nanometer drug delivery system, and application thereof

Abstract

The invention discloses a preparation method of an oxidoreduction responsiveness tumor-targeted cis-platinum nanometer drug delivery system, and application thereof, relates to the building and the preparing of a high-load cis-platinum macromolecule pro-drug and a hyaluronic acid-coated high-load cis-platinum nanometer drug delivery system, and can be applied to active targeting treatment of tumors. Polyethyleneimine is adopted as a framework, and cystamine containing a disulfide bond with oxidoreduction responsiveness is selected to be reacted with butanedioic anhydride so as to be complexedwith cis-platinum, so that a cis-platinum complex is obtained. The obtained cis-platinum complex and the polyethyleneimine are covalently bonded to obtain the high-load cis-platinum macromolecule pro-drug, and a hyaluronic acid targeted group is coated on an outer layer, so that the oxidoreduction responsiveness tumor-targeted cis-platinum nanometer drug delivery system with a tumor active targeting function is obtained. Compared with traditional chemotherapy drug cis-platinum, the oxidoreduction responsiveness tumor-targeted cis-platinum nanometer drug delivery system provided by the invention can realize tumor active targeting drug delivery and oxidoreduction responsiveness drug release, plays a role in anti-tumor treatment, is capable of effectively reducing the toxic and side effects caused by the cis-platinum on other visceral organs of a body, and has a favorable clinic application prospect.

Description

technical field

[0001] The invention relates to a preparation method of a high-load cisplatin polymer prodrug and a hyaluronic acid-coated redox-responsive tumor-targeting nano-drug delivery system, which can be used for the treatment of tumors. Background technique

[0002] Cisplatin (Cisplatin) is cisplatin dichlorodiamminoplatinum. As a platinum antitumor chemotherapy drug, it has shown good antitumor effect in clinical treatment after being approved by the US FDA. It is widely used in ovarian cancer, prostate cancer, testicular cancer, etc. Cancer, lung cancer, nasopharyngeal cancer, esophageal cancer, breast cancer and other tumors. After cisplatin enters the cell, a dissociation reaction occurs in the cell to generate hydrated complex ions, which are transported to the nucleus, bind to the DNA in the nucleus, hinder DNA replication, and cause cell apoptosis and necrosis. The effect of cisplatin on DNA replication is non-specific, so cisplatin has strong systemic side ...

Images