Construction Of Multifunctional Polypyrrole Drug Nano-carrier System And Its Application In Cancer Therapy

Smart responsive nanomedicine which combines various therapeutic and diagnostic functions exhibits attractive application prospect in the field of cancer theranostic,for its low side effects,specific tumor targeting,controllable drug releasing and excellent theranostic properties.Polypyrrole nanoparticles(NPs),a new generation of photothermal nanoagent,owing to their meglio biocompatibility,photothermal property and imaging property,were widely used for constructing smart responsive nanomedicine.However,the lack of surface functional groups,insufficient tumor targeting property and nondegradable in vivo hindered the application of PPy NPs.For the above problems,PPy NPs were chosen herein as research objects.The corresponding research work mainly focused on the preparation of PPy NPs with abundant surface functional groups,meglio tumor cell uptake efficiency and degradable property.The main research contents are as follow:(1)The preparation of functional PPyCOOH nanoneedles(NNs)and their application in PDT/PTT combined therapy for cancerHerein,Zeta potential and size matched PPyCOOH NNs and PPyCOOH nanospheres(NSs)were prepared using Py-3-COOH as conductive polymer monomer.Compared with typical PPyCOOH NSs,PPyCOOH NNs were found to exhibit higher cell uptake efficiency.After loading PPyCOOH NNs with aluminum phthalocyanine tetrasulfonate(A1PCS4)and modified with polyallylamine hydrochloride(PAH)and polyacrylic acid(PAA),nanoneedle complexes(A1PCS4@PPyCONH-PAH-PAA)integrating photodynamic therapy(PDT)and photothermal therapy(PTT)were successfully fabricated.The as-prepared NNs complexes can effectively enhance the cell uptake efficiency and tumor targeting property of A1PCS4 according to the cell and animal experiment results.Moreover,AlPCS4@PPyCONH-PAH-PAA was verified to own excellent biocompatibility and PDT/PTT synergistic curative effects.The as-prepared PPyCOOH NNs not only possess abundant carboxyl groups,but also exhibited excellent cell uptake efficiency,which broadened the application of PPy NPs in the field of cancer theranostic.(2)Construction of pH/H2O2 dual responsible drug loading system based on PPyCOOH NPs and their application in chemotherapy/PTT combined therapy for cancerHerein,novel PAA@PPyCOOH NPs which can be degraded under tumor H2O2 microenviroment(0.1?1mM)were prepared using polyacrylic acid(PAA)as template molecule and Py-3-COOH as conductive polymer monomer.After loading doxorubicine hydrochloride(DOX-HCl),a positive charged chemotherapeutics,onto PAA@PPyCOOHNPs via electrostatic adsorption,PAA@PPyCOOH@DOXNPs with chemotherapy/PTT combined curative effects and pH/H2O2 dual responsible drug releasing property were successfully obtained.According to the drug release experiment,the ultimate drug release percentage of PAA@PPyCOOH@DOX NPs in simulate tumor microenviroment(PBS 7.4+1 mM H2O2,PBS 6.5+1 mM H2O2)were 1.8 and 2.1 fold of that in PBS 7.4(37%)during 3 days,respectively.Moreover,we found in the cell and animal experiments that as-prepared PAA@PPyCOOH@DOX NPs could effectively be internalized by tumor cells with improving tumor targeting property of DOX,and exhibited excellent biocompatibility and chemotherapy/PTT synergistic curative effects.The PAA@PPyCOOH@DOX NPs prepared herein not only possess functional groups and excellent drug loading property,but also were degradable under the tumor H2O2 microenviroment,indicating that PAA@PPyCOOH NPs were promising drug nanocarriers.(3)Preparation of biodegradable PPy@PyCOOH hollow nanosphere and its application in PDT/PTT combined therapy for cancerHerein,a novel PPy@PyCOOH hollow nanosphere which can be biodegraded under tumor H2O2 microenviroment(0.1?1mM)were prepared by copolymerizing pyrrole and Py-3-COOH using FeCl2/H2O2 as oxidant system via a one-pot free template method.After modification by bovine serum albumin(BSA)and further loading with PDT drug IR806,hollow nanosphere complexes(PPy@PyCONH-BSA@IR806)with PDT/PTT synergistic curative effects were successfully prepared.According to the cell and animal experiments,PPy@PyCONH-BSA@IR806 can not only realize single laser induced PDT/PTT combined therapy,but also have infrared thermal and fluorescent imaging properties and its degradation products can be excreted out the mice body,exhibiting excellent theranostic property and biosecurity.