Application And Research Of Disulfiram/Cu²⁺ Co-delivery Carrier With Targeting Effect

In the past decades,researchers have been trying to treat cancer,but cancer is still one of the most lethal diseases.As an important treatment,chemotherapy still has some disadvantages,such as poor curative effect and large side effects.In order to avoid the permanent harm of chemotherapy drugs to human body,scientists try to develop nano drug carriers.Micelles have unique pharmacokinetic properties,and their biological distribution in vivo can be changed by enhanced permeation and retention（EPR）effect.In addition,some compounds with specific targeting effect on tumor cells can be modified on the surface of micelles to enhance the active targeting ability of micelles.In this study,we designed a pH responsive nanocarrier based on hyaluronic acid（HA）to deliver disulfiram（DSF）and Cu²⁺.Firstly,polycaprolactone（PCL）was synthesized by ring opening polymerization.HA-PEG-PCL grafted polymer was prepared by modifying HA with hydrophilic polymer,polyethylene glycol monomethyl ether（MPEG）and hydrophobic polycaprolactone.Then,through the hydrophobic interaction of HA-PEG-PCL,DSF was loaded into the polymer to form nano micelles（HPPD）.Finally,the topological structure of carboxyl and Cu²⁺on the surface of HPPD was used to carry exogenous Cu²⁺synthesis（HPPDC）.The topological structure of Cu-O in HPPDC not only reduces the biological toxicity but also has a positive effect on killing cancer cells.The Cu²⁺on HPPDC will fall off,the crosslinked structure will disintegrate and release DSF in the micelle,so as to cooperate with anticancer.In this study,the carrier polymer was characterized,and the particle morphology and in vitro release were characterized.And carried out anti-tumor activity experiments at the cellular and animal levels.Cell and animal experiments show the superiority of HPPDC in anticancer.The anti-cancer effect of HPPDC combined with DSF and Cu²⁺is better than that of HPPD.It can be used for reference in clinical application of DSF.