The Research Of The Fluorescence Probe And Nano-drug Based On The Polyethyleneimine-coated Quantum Dots

For a long time,chemotherapy,as the main method of cancer treatment,generally has some shortcomings,such as poor targeting,high toxicity,obvious side effects,and so on.As a new type of drug delivery system,nano-drug carriers show great potential and advantages in cancer treatment because of their unique chemical properties and enhanced permeability and retention effect(EPR effect).Therefore,the development of nanomaterials as the carrier of anticancer drugs to improve the targeting of anticancer drugs and reduce side effects is a new method for the treatment of cancer.Quantum dots(QDs)is a new type of semiconductor nanoparticles with small particle size and stable properties.Because of its unique optical properties such as long fluorescence lifetime,strong anti-bleaching ability and good biocompatibility,QDs plays an important role in material science and biomedicine.Polyethyleneimine(PEI)is a common macromolecular polymer,which is rich in amino groups and has good water solubility.Because it has a large number of amino groups in its structure,it has a rich positive charge and has a strong chelating effect with metal ions.And PEI is cheap and effective,so it is widely used as a carrier.In this paper,PEI was used to modify the QDs,and the functionalized water-soluble QDs were obtained.The main research as follows:1.We prepared Cd Se and Cd Se/Zn S QDs coated by trioctylphosphine oxide(TOPO),and then QDs were modified with PEI(1.8 k Da),hydrophilic QDs with uniform dispersion and stable properties was obtained.Due to the abundant positive charge on the surface of PEI,the negatively charged mitochondriaprobe small molecule(3-carboxypropyl)triphenylphosphine(TPP)were loaded by electrostatic adsorption.The modified QDs were characterized by transmission electron microscope(TEM),ultraviolet absorption spectrum(UV-Vis)and fluorescence spectrometer(PL).Polyethyleneimine-(3-carboxypropyl)triphenylphosphine modified QDs were used to treat He La and A549 cells.MTT results showed that the cytotoxicity of the modified QDs was less,and the IC50 of Cd Se/Zn S@PEI-TPP on A549 cells was more than 300 ?g/m L.The fluorescence imaging of the modified quantum dots was studied by laser confocal fluorescence microscope,and it was found that the fluorescence intensity of the modified quantum dots was very strong in He La cells and A549 cells.The co-localization of mitochondrial fluorescent dye Mito-Tracker Green and modified QDs Cd Se/Zn S@PEI-TPP was also studied by confocal fluorescence microscope.It was found that the modified quantum dots completely coincided with mitochondrial fluorescent dyes,indicating that the modified quantum dots could target mitochondria,which is expected to be a new type of mitochondrial fluorescent probe.2.Cd Se and Cd Se/Zn S QDs were modified by PEI(1.8 k Da),and PEI-coated quantum dots were obtained.Then 10-hydroxycamptothecin(HCPT)was connected with hydrophilic succinic acid by biodegradable ester bond to obtain HCPT derivative c HCPT,and then covalently linked with PEI-modified QDs by amide bond to obtain QDs@PEI-c HCPT.The modified QDs were characterized by TEM,UV-Vis and PL.It was found that the modified QDs had good water solubility and stable properties.The cytotoxicity of QDs to He La,HCT-116,QSG-7701 and A549 cells was studied by MTT method.It was found that the modified quantum dots could inhibit the growth of He La cells more effectively than other cells.Apoptosis plays an important role in the inhibition of cell proliferation by Cd Se/Zn S@PEI-c HCPT,which was confirmed by some apoptotic index experiments,such as Annexin V/PI,mitochondrial membrane potential(MMP)analysis,reactive oxygen species(ROS)analysis and acridine orange/ethidiumbromide(AO/EB)staining.More importantly,Cd Se/Zn S@PEI-c HCPT can effectively induce apoptosis by down-regulating the expression of Bcl-2 protein and increasing the expression of P53,Bak and PARP-1.In addition,we also studied its anti-tumor activity in animals.The results show that Cd Se/Zn S@PEI-c HCPT can effectively inhibit tumor proliferation in mice and achieve better results than HCPT.Therefore,Cd Se/Zn S@PEI-c HCPT drug delivery system is a new type of nano-drug delivery system,which provides a new idea for the construction of a new nano-drug delivery system.