Synthesis And Antitumor Activity Of CdSe/ZnS Quantum Dot Nano-Drug Carriers

The diagnosis and treatment of cancer is currently one of the hot spots in the research of medical workers.The main treatment methods for cancer are:surgery,chemotherapy,radiotherapy,biological immunotherapy.Chemotherapy is the most common and effective way to treat tumors,but most chemotherapy drugs are insoluble in water,poorly targeted,and toxic to normal cells,so the side effects are very obvious.The emergence of nanodrug carriers that can achieve targeted tracing therapy solves this problem,among which inorganic nanomaterial quantum dots are more commonly used.Quantum dots have excellent physical and optical properties,and the specific surface area of quantum dots is large and the surface is easy to modify,which makes quantum dots widely used in biomedical aspects such as targeted drug carriers,disease diagnosis,and biological imaging.In this paper,we first synthesize CdSe/ZnS quantum dots with uniform particle size and high fluorescence quantum yield,and then modify the quantum dots by ligand exchange method to obtain quantum dot water-soluble modifiers,and then connect anticancer drugs and targeted polypeptides to obtain a nano-drug carrier system with fluorescent tracer and targeted therapeutic effect,and then study it:1.We synthesized CdSe/ZnS quantum dots by organic synthesis,then modified the oil-soluble quantum dots to be water-soluble with dihydrohipoic acid（DHLA）,and then PEG₂₀₀₀ was connected by ester bond to increase the biocompatibility of the whole system and prolong the circulation time of nano drugs in vivo.At the same time,10-hydroxycamptothecin（HCPT）was connected with hydrophilic succinic acid through ester bond to obtain 10-hydroxycamptothecin derivative c HCPT,and then the derivative was covalently connected with modified quantum dots through ester bond to obtain HCPT loaded nano drug loading system CdSe/ZnS@DHLA-PEG-HCPT。By ultraviolet absorption spectrum（UV-vis）,fluorescence spectrometer（FL）,infrared spectrophotometer（IR）,transmission electron microscope（TEM）,Zeta potentiometric analyzer and other instruments were detected and analyzed,and the results proved that the CdSe/ZnS@DHLA-PEG-HCPT nanocarriage system was successfully synthesized.The results of cytotoxicity experiment showed that the cytotoxicity of carrier CdSe/ZnS@DHLA-PEG was very small,while CdSe/ZnS@DHLA-PEG-HCPT nano drug delivery system showed a good inhibitory effect on tumor cells.The flow cytometry results show that the nano-drug carrier system can reduce the mitochondrial membrane potential of tumor cells,induce apoptosis of cells,promote autophagy,and achieve the effect of inhibiting tumor cell proliferation.The results of laser confocal experiment showed that the fluorescence intensity in cells increased with the increase of CdSe/ZnS@DHLA-PEG-HCPT concentration,which showed that the cell uptake was directly proportional to the concentration of nano drugs.Finally,we established a mouse tumor model for tumor inhibition experiment.The experimental results showed that the antitumor effect of the nano drug loading system was significantly better than that of the positive drug HCPT,and the tissue H&E staining results showed the nano drug loading system showed low toxic and side effects on other tissues and organs.Therefore,CdSe/ZnS@DHLA-PEG-HCPT is a nano-drug carrier system with good anti-tumor effect and low toxicity,and has good application prospects in the direction of nanocarriage.2.We synthesized macromolecule hyperbranched polyamide amines（HPAMAMAM）with multiple amino groups,and then modified to the surface of CdSe/ZnS quantum dots to obtain CdSe/ZnS@HPAMAM with good water solubility.Then the positive drugs?-tocopheryl succinate（?-TOS）and paclitaxel（PTX）were successively loaded to obtain a dual-carrier drug nanocarriage system（CdSe/ZnS@HPAMAM-?-TOS）-S-S-PTX,and finally modified the liver cancer targeting polypeptide 9R-P201 to obtain a nanocarribulum carrier system with hepatocellular carcinoma targeting effect（CdSe/ZnS@HPAMAM-?-TOS）-S-PTX-9R-P201,and the nano drug loading system was characterized by UV and TEM.Cytotoxicity experimental results showed that the nano-drug carrier system（CdSe/ZnS@HPAMAM-?-TOS）-S-S-PTX-9R-P201 showed good targeted therapy effect on Hep G2,and the inhibition of cells is significantly better than that of SNU-739 cells.In addition,the dual-load drug system(CdSe/ZnS@HPAMAM-（?-TOS）-S-S-PTX also exhibited a better inhibition effect on tumor cell proliferation than single-carrier systems CdSe/ZnS@HPAMAM-?-TOS or CdSe/ZnS@HPAMAM-SS-PTX.Flow cytometry results showed that the drug carrier system（CdSe/ZnS@HPAMAM-?-TOS）-S-S-PTX-9R-P201 induced apoptosis,enhanced autophagy,reduced the mitochondrial membrane potential of cells,and increased the active oxygen species content in cells better than other drug carrier systems.For the constructed mouse liver cancer tumor model,the drug carrier system（CdSe/ZnS@HPAMAM-?-TOS）-S-S-PTX-9R-P201 showed a good effect of inhibiting tumor growth,and there were no obvious toxic side effects.In addition,the results of in vitro fluorescence imaging of mouse organ tissues showed that within 24 h of administration,the fluorescence intensity in mouse tumor tissues showed a tendency to first increase and then decrease,of which the fluorescence intensity in tumor tissues reached the strongest at 12 h of administration This indicates that the drug reaches its maximum aggregation in the tumor tissue at 12 h,after which the drug is gradually metabolized out of the body.In short,the nano-carrier drug system has a good targeted inhibition effect of liver cancer tumors,as well as a better dual-load drug synergistic treatment effect,which is tumor treatment Ways offer a new approach.