Preparation Of Multifunctional Targeting Nanomaterials And Its Application In Tumor Threapy

There are many problems in clinical cancer treatment at this stage,such as poor efficacy and high toxic and side effects.Photothermal therapy as a new type of minimally invasive therapy can largely solve this problem.The paper mainly introduced the preparation of two kinds of multi-functional targeting nanomaterials and their application in the cancer therpay.The specific research contents are as follows:（1）We fabricated a novel multifunctional nanocomposite,PS@CS@Au-Fe₃O₄-FA/ICG（polystyrene@chitosan@gold nanoparticles-Fe₃O₄nanoparticles-folic acid/indocyanine green）,which can be used for CT,MR and fluorescence imaging guided targeted-photothermal therapy of cancer cells.First,chitosan（CS）was coated on the polystyrene because of electrostatic adsorption between carboxyl in PS and amino of CS,followed by gold particles and iron oxide particles growing on the surface due to amino of CS adsorbing metal ion.Next,folic acid（FA）was linked to the outside of PS@CS@Au-Fe₃O₄ by covalent coupling of amino in CS and carboxyl in FA,obtaining PS@CS@Au-Fe₃O₄-FA,which can load electronegative ICG by electrostatic adsorption.The constructed PS@CS@Au-Fe₃O₄-FA/ICG nanocomposites possessed excellent computed tomography,magnetic resonance and fluorescence imaging performances which could be used to diagnose tumor and monitor the nanocomposites’localization in vivo.Moreover,PS@CS@Au-Fe₃O₄-FA/ICG nanocomposites can be targetedly delivered to cancer cells by folic acid through receptor mediated way,and tumor growth could be efficiently inhibited even completely ablated under NIR irradiation.That is,the constructed PS@CS@Au-Fe₃O₄-FA/ICG biomaterial was vindicated a great potential for computed tomography,magnetic resonance and fluorescence imaging performances which could be used to diagnose tumor and monitor the nanocomposites’local and fluorescence imaging guided targeted therapy of cancer cells.（2）We fabricated ultrasmall Se particles@porous silica-folic acid-copper sulfide nanocomposites（Se@Si O₂-FA-Cu S NCs）to load DOX,which demonstrated synergistic combination of chemo-phototherapy for cancer treatment.The detailed synthesis procedure and application in tumor therapy was displayed in Scheme 1.Se@Si O₂ spheres were firstly synthesized according to our previous method.42 Then the surface of Se@Si O₂ spheres were modified with amino（NH₂）.Subsequently,the spheres were treated with hot water to form porous structures.Finally,folic acid（FA）targets were connected and Cu S NPs were adsorbed onto the surface of porous Se@Si O₂ spheres by electrostatic adsorption.Nano Se could be released from the Se@Si O₂ spheres and DOX could be loaded through the porous channel.Se@Si O₂-FA-Cu S/DOX nanocomposites could be assembled in tumor through the targeted delivery by FA group.Photothermal therapy could be driven under NIR irradiation due to Cu S NPs of Se@Si O₂-FA-Cu S/DOX nanocomposites.At the same time,DOX and Se were released from Se@Si O₂-FA-Cu S/DOX nanocomposites for chemotherapy.The three therapy approaches demonstrated synergetic effect,which could efficiently inhibit cancer cells,even completely eliminate tumor.In addition,Se could reduce the toxicity of DOX,and the treatment of Se@Si O₂-FA-Cu S/DOX nanocomposites exhibited no appreciable adverse reactions.Thus,Se@Si O₂-FA-Cu S/DOX nanocomposites have great potential as a multifunctional nanoplatform for combining photothermal and chemotherapy for cancer treatment.In this paper,nanocarriers were ingeniously assembled by targeting agent（based FA,an active targeting ligand）and photothermal reagents,combining imaging,photothermal therapy and chemotherapy.Those nanocarriers combine the diagnosis and therapy,which have excellent application in the field of cancer therapy.