Preparation And Characterization Of Conducting Polymer-loaded Polyglutamic Acid Nanogels For Theranostic Applications

The development of nanoscience and nanotechnology makes it possible to continually explore new effective and safe strategies for the diagnosis and therapy of cancer.Photoacoustic?PA?imaging and photothermal therapy?PTT?have attracted much attention due to their advantages such as high efficiency,non-invasion and fewer side effect.The photoacoustic contrast agents and photothermal agents are usually composed of organic or inorganic materials with strong near-infrared absorbance.Compared to inorganic material,conducting polymer photothermal agents are safer and easier for clinic applications.However,there are still great challenges in efficiently transporting the conducting polymers to the tumor site for subsequent endocytosis.In our previous work,Fe₃O₄ was loaded in polyglutamic acid??-PGA?nanogels by double emulsion method,endowing better uptake of Fe₃O₄ by tumor cells to make better MR imaging capability.In this study,taking advantages of the stability and flexibility of?-PGA,conducting polymer polyaniline?PANI?or polypyrrole?PPy?were loaded to form two types of novel?-PGA nanogels?NGs?for enhanced PA imaging and PTT of tumors.In Chapter 2,we prepared PANI loaded?-PGA nanogels for PA imaging and PTT of tumor.?-PGA W/O/W polymer emulsion was first formed via a double emulsion approach,followed by crosslinking with cystamine dihydrochloride?Cys?to generate?-PGA nanogels.Then?-PGA nanogels were used as a“nanoreactor”to load aniline by electrostatic interaction,and?-PGA/Cys@PANI NGs were synthesized by in situ polymerization under catalyzation of ammonium persulfate?APS?.The?-PGA/Cys@PANI NGs with an average size of 71.9±15.8 nm are dispersible in water,colloidally stable,and cytocompatible and hemocompatible in the concentration range studied.The strong near-infrared?NIR?absorbance renders the NGs with good PA imaging contrast enhancement and photothermal conversion properties that can be used for photothermal therapy in vitro cancer cells and tumor xenograft.In Chapter 3,we explored the use of PPy-loaded?-PGA NGs for tumor PA-imaging-guided PTT.First,we synthesized the?-PGA/Cys NGs by using the same method in the second chapter.Then,PPy-loaded?-PGA/Cys NGs were synthesized by in situ oxidation polymerization using FeCl₃ as catalyst.The size of?-PGA/Cys@PPy NGs is 38.9±8.57 nm.The stability experiment shows that the NGs have good water solubility and colloidal stability.The strong near-infrared?NIR?absorbance renders the NGs with good PA imaging contrast enhancement and photothermal conversion properties that can be used for photothermal therapy in vitro cancer cells and tumor xenograft.In addition,we also investigated the effects of combination of radiotherapy?RT?and PTT as well as the treatment sequence of RT and PTT on the therapy of tumor xenograft.In conclusion,we synthesized the Cys crosslinked?-PGA NGs by double emulsification and?-PGA/Cys NGs were used to load PANI or PPy nanoparticles for PA imaging and PTT,respectively.The nanomaterial design thoughts and findings from this study provide new ideas to develop novel effective and safe theranostic nanoplatform,for example the above nanoplatform may be used to further load other imaging or/and therapeutic elements,or be modified with functional groups?such as targeting ligands?for theranostic applications of tumor.