Design And In Vitro Evaluation Of Traceable Nano-prodrug Based On Fluorescent Carbon Quantum Dots

At present,chemotherapy is the main auxiliary method in cancer treatment.As a cytotoxic drug,chemotherapy drugs have many shortcomings,such as poor water solubility,no specific targeting for cancer cells,easy to be cleared by the kidney,and easy to cause the body drug resistance,etc.which will reduce its anti-cancer activity.Therefore,in order to reducing the toxic and side effects of the drug during treatment,the drug delivery system designed should not only be stimulate responsive,but also can specifically identify normal tissues and tumor tissues to achieve low or zero release under physiological conditions and high release under the tumor cell microenvironment.In addition,the introduction of fluorescent substances such as carbon quantum dots into the drug delivery system can achieve real-time monitoring of tumor tissue,and then achieve the purpose of real-time drug administration and guided treatment.So,this paper focused on the research of traceable nano-prodrugs based on fluorescent carbon quantum dots.This thesis mainly includes the following parts:1.The pH-sensitive nano-prodrug C-CDs_PEG-Hy-DOX with tumor-specific fluorescence properties was designed.The stable nano-prodrug had low leakage and shown weak fluorescence in normal physiological media while in in the tumor cell microenvironment,once DOX was released,the fluorescence of carbon quantum dots would be recovered,which indicated that it had the potential for real-time fluorescence monitoring treatment during tumor treatment.MTT experiments showed that the drug carrier was biocompatible and the prodrugs had strong inhibitory effects on cancer cell proliferation.2.By using a hydrophobic DOX which coupled carbon quantum dot as the nucleus of comet and a small amount of hydrophilic reducible and degradable polyethylene glycol brush as the comet tail,the pH/reduction dual-response nano-microsphere was obtained and after its self-assembly,we achieved a high-content prodrug called DOX-Hy-CQD-SS-PEG.The inhibitory effect of the nano-prodrug on cancer cells was better than DOX,and the nano-drug carrier had good biocompatibility,its structure was completely disintegrated after the release of DOX,meanwhile the nano-prodrug shown pH/reduction dual-responsive drug release performance with low drug release rate under physiological conditions.In addition,fluorescent carbon quantum dots can recover fluorescence intensity after releasing DOX,indicating its potential application in real-time cancer treatment.3.The pH/GSH dual-responsive polymer nano-prodrug PEG-PO-Cy@CDs-Hy-DOX could be obtained through using reduction-responsive carrier PEG-PO-Cy and acid sensitive nano-prodrug CDs-Hy-DOX after self-assembly.which showed strong inhibitory effects on tumor cell proliferation.The drug carrier would disintegrated and the acid-sensitive prodrug could be released to achieve a high drug release rate under the condition of high concentration of GSH in tumor tissue.What's more,the carrier itself showed good biocompatibility.At the same time,the fluorescence of carbon quantum dots could be recovered after the releasing of DOX,making it display great application potential in the controlled release of anticancer drugs and real-time fluorescence imaging of tumor tissues.