The Synthesis Of Biocompatible Polyaniline-based Composite Nanoparticles And Their Application In Effectively Targeted Photothermal Therapy Using NIR

Chapter 1:The construction of advanced phototherapy systems with high therapeutic efficacy and low side effect toward cancer,especially targeted species,is highly desirable.The research progresses of photothermal reagents for photothermal therapy are summarized.Especially we focused on polyaniline,which has a good biocompatibility,high photothermal conversion efficiency,and potential application prospects as photothermal agents.In the end,the significance and highlights of this article are proposed.Chapter 2 and 3:One kind of water-soluble hyaluronic acid-hybrided polyaniline nanoparticles(HA-PANI NPs)was synthesized as a nanoplatform for photothermal therapy(PTT)with targeted specificity of CD44-mediated cancer cell.The water-soluble HA-PANI NPs were fabricated by one-step oxidative polymerization using aniline as polymerized monomer and HA as a stabilizer and targeted agent,where non-covalently electrostatic interaction between the negatively charged polymer HA and the cationic polymer PANI drives the formation of HA-PANI NPs.The results of atomic force electron microscope(AFM),scanning electron microscopy(SEM),dynamic light scattering(DLS)and Zeta potential demonstrated that near spherical HA-PANI NPs are well-dispersed in aqueous solutions,with average hydrodynamic diameter around 100 nm.The thermal imaging camera recorded that the temperature of the aqueous solution of HA-PANI NPs increased 40.1℃ upon exposure to an 808 nm(2 W cm-2)laser for 10 min.The each quantity of HA and PANI in HA-PANI NPs was calculated by TGA,which were 16%and 84%,respectively.In addition,the targeted photothermal therapy efficacy of tumor cells was studied by HA-PANI NPs in vitro and vivo.In vitro,HA-PANI NPs shown negligible cytotoxicity,revealed that they can selectively kill CD44-mediated cancer cells rather than normal cells via exposure to a NIR 808 nm laser.The efficient intracellular targeted intake of the HA-PANI NPs by both HeLa and HCT-116 cells are observed by UV-Vis-NIR assay,indicating their targeted ability for CD44-overexpressing cancer cells.Furthermore,in vivo photothermal ablation of tumor with excellent treatment efficacy was achieved.In a brief summary,these results highlight that HA-PANI NPs can be considered as an extremely promising material for targeted PTT of cancer.Chapter 4:Poly(N-phenylglycine)(PGNP),a conductive polymer with a similar structure to polyaniline,has not been reported as a photothermal therapy agent nowadays.In this chapter,NH2-PEG-NH2 were used to combine PGNP with HA by amide reaction.The water-soluble PGNP-PEG-HA nanoparticles were synthesized.The results of SEM,TEM and Zeta potential demonstrated that approximately spherical PGNP-PEG-HA are well-dispersed in aqueous solutions,with an average diameter around 70 nm.The graft ratio is 1:1:9 between PGNP,PEG and HA monomer,as calculated by 1H NMR.The thermal imaging camera recorded that the temperature of the aqueous solution of HA-PANI NPs increased 33.4℃ upon exposure to an 808 nm laser for 5 min.In addition,the targeted photothermal therapy efficacy of tumor cells was studied by PGNP-PEG-HA in vitro and vivo.In vitro,PGNP-PEG-HA shown negligible cytotoxicity in vitro,revealing that PGNP-PEG-HA can selectively kill CD44-mediated cancer cells.Furthermore,in vivo photothermal ablation of tumor with excellent treatment efficacy was achieved.In this work,we have synthesized water-soluble PGNP-PEG-HA nanoparticles with both good physiological and environmental stability and high thermal conversion efficiency by a covalent linking.More important,as photothermal therapy agents,PGNP canact as a multifunctional platform by the modification of carboxyl group.In summary,PGNP-PEG-HA is an extremely promising photothermal agent.