Study On Synthesis,Characterization Of Metallic Nanoparticles And Their Anti-Tumor Property

Tumor therapy is one of the major challenges in the field of medicine.Traditional therapy strategies of tumor are chemotherapy,radiotherapy and surgery,limited by drug resistance and toxic side effects.In comparison with small molecular drugs,nanomedicine has obvious advantages that it has physical dimensions and the surface chemistry properties in the clinical application.Inorganic nanomaterials have attracted attention by low toxicity and controllable size and were often used in targeting therapy,drug delivery system and thermotherapy,such as:MRI(Fe3O4 NPs),catalysis and photothermal therapy(CuS NPs and Au NPs).The advancement of nanomedicines is mainly attributed to the ability of intravenously administered nano-sized particles having a more favorable distribution within the body compared to molecules.However;in many cases the ability of nanomedicines to increase a patient' s survival or quality of life have been marginal.Marginal improvements are a result of a series of biological obstacles which prevent a nanomedicine from achieving its full potential.These obstacles include:(1)opsonization;(2)the ability of the particles to home to disease sites;(3)the stability of nanoparticles and the ability of the particle to be internalized by a cell.In this work,we designed a series of functional inorganic nanoparticles,hoping to increase the accumulation of nano-drugs in tumor to solve the problems of nanoparticles in tumor therapy.The aim of these research is as follows:(1)Considering the effect of surface chemistry on distribution of nanoparticles in vivo,we designed and synthesized an extremely low immunogenicity poly(2-methyl-2-oxazoline)(PMOZ).In this work,to improve the half-life of nanoparticles,the PMOZ modified gold nanoparticles(Au-PMOZ NPs)that it's as a model were investigated.As a result,Au-PMOZ NPs has similar stability,biocompatible and circulation time compare to PEG modified gold nanoparticles(Au-PEG NPs).After second injection of polymer modified gold nanoparticles,the alternating treatment of Au-PEG NPs and Au-PMOZ NPs could avoid the accelerated blood clearance phenomenon(ABC),resulting prolonging the circulation half-time,minimizing the accumulation of non-target organs and improving the efficacy of therapy.(2)Since the overexpression of epidermal growth factor receptor(EGFR)on tumor cells,this could be as a favorable target for tumor therapy.Cetuximab(Ab),a targeting ligand of EGFR,has been used as an antitumor drug in clinical applications.Ab was modified to CuS NPs which had excellent photothermal conversion efficiency in near-infrared ? window to increase the accumulation of nanoparticles in tumor.As depicted in result,CuS-Ab NPs could increase the accumulation of nanoparticles in tumor and lower the damage of normal tissue by photothermal therapy(PTT).According to the result of immunohistochemical analysis(IHC),CuS-Ab NPs exhibited superior in anti-angiogenesis than CuS NPs.Combine with irradiation of laser,the CuS-Ab NPs could inhibit the tumor development,indicating the combination of anti-angiogenesis and PTT could enhance the efficacy of anti-tumor.(3)Traditional therapy strategies of tumor are chemotherapy,radiotherapy and surgery,limited by drug resistance and toxic side effects.Nanomedicine have attracted attention by prolonging circulation half time and minimizing system toxicity.The gold nanorods(GNRs)were synthesized as pioneering reported.The mPEG-SH was modified with GNRs to reduce the toxicity of hexadecyltrimethylammonium bromide(CTAB).And then,the dopamine,which is an excellent biocompatible molecular,was added into GNR@PEG solution at pH 8.5 to synthesize the nanocomposite(GNR@PD).Doxorubicin(DOX)was adsorbed on the surface of GNR@PD via electrostatic and/or?-? stacking interactions,forming GNR@PD-PEG-DOX nanocomposites.When the nanocomposites arrived to tumor environment,the DOX was released from GNR@PD-PEG-DOX depended on the pH value.In addition,the GNRs,as a PTT agent,has excellent photothermal conversion efficiency.In general,the nanocomposites accumulate in tumor site through enhanced permeability and retention effect(EPR effect)after intravenous injection.The temperature of tumor has increase quickly when the tumor was exposed to laser.With the combination of chemotherapy and PTT,the tumor ablation was happened in GNR@PD-PEG-DOX group.Importantly,the metastasis was effectively inhibited by GNR@PD-PEG-DOX.