The Preparation Of Mn-DOX Metal-organic Nanoparticles And Their Integrated Research On Anti-tumor Diagnosis And Treatment

In recent years,the living standards of people have gradually improved but cancer has seriously affected human health.In clinical treatment,traditional anti-cancer treatments often bring serious toxicity and low treatment efficiency.The nano drug carriers in drug delivery systems can not only increase the amount of drug accumulation in tumor and the utilization rate of drugs but also reduce the side effects of drugs on the human body.Doxorubicin?DOX?as one of the most widely used anti-cancer drugs,plays a vital role in the treatment of a range of tumors.However,the severe toxicity and side effects of DOX limit its clinical useing.In this paper,we modified the traditional organic small molecule drug doxorubicin?DOX?,and prepared a novel Mn-DOX@DSPE-mPEG2000 miceller nanoparticles?MDDM NPs?by a simple nano-sedimentation method.We conducted a series of characterizations on this nanoparticles and tested its antitumor activity in vivo and in vitro as well as its biological toxicity.Based on the above content,the main work and results of this paper are as follow:?1?Doxorubicin?DOX?as a therapeutic drug was coordinated with Mn²⁺to obtain Mn?DOX?₂ hydrophobic core.Then the outer layer of Mn-DOX was coated with amphiphilic block copolymer DSPE-mPEG2000 by self-assembly and eventually obtained the stable Mn-DOX@DSPE-mPEG2000?MDDM?miceller nanoparticles in water.The nanoparticles has showed good dispersibility and stability.Since DOX formed the metal complex,its toxicity was much lower than free DOX and the hydrophilic PEG shell also provided excellent biocompatibility and stability.And the size of nanoparticles was about 80nm,which can be accumulated in the tumor by passive targeting.The nanoparticles could release the drug by pH responsive.?2?For the synthesized MDDM nanoparticles,we conducted a series of in vivo and in vitro characterizations for its antitumor activity and biological toxicity.The MTT experiments have showed that MDDM nanoparticles have a certain inhibitory effect on HeLa tumor cell proliferation,while no obvious toxicity on NIH3T3 normal cells.The cellular uptake and localization experiment has showed that MDDM nanoparticles could be readily transported into tumor cells in a short time.And in vivo animal experiment,the treatment of tumor-bearing mice by intravenous injection has indicated that MDDM nanoparticles have great biocompatibility and excellent antitumor efficiency.At the same time,due to the coordination of Mn²⁺,the MDDM nanoparticles could be an effective contrast agent for magnetic resonance?MR?imaging and track drug treatment.Those work provides a certain reference for the study of the coordination of drugs and metals to reduce toxicity meanwhile provide metal functions.