Construction Of Polydopamine/Fenton-like Nanoplatforms For Tumor Therapy Applications

Chemodynamic therapy（CDT） is a promising antitumor therapy strategy that utilizes iron-mediated Fenton reaction to transform endogenous hydrogen peroxide（H₂O₂）into hydroxyl radical（·OH）,resulting in cell death.However,the rate of iron-based Fenton reaction is often limited by the acidity of tumor microenvironment（TME）and glutathione（GSH）overexpression.Therefore,how to improve the yield of·OH and enhance the therapeutic effect of CDT is an urgent problem to be solved at present.In this study,we successfully constructed two polydopamine（PDA）/Fenton-like reagents composite nanoplatform to enhance the effect of CDT by increasing the temperature of the catalytic reaction and removing GSH in tumor cells,thus achieving enhanced antitumor effect.The main contents of this paper are as follows:1.Firstly,a polydopamine/copper multifunctional nanoplatform was constructed to achieve tumor cell ablation using photothermal enhanced chemodynamic therapy strategy.PDA nanoparticles were prepared through the self-polymerization method,which were subsequently chelated with Cu（Ⅱ）and linked with Polyethylene glycol（PEG）chains,finally obtaining PDA-Cu（Ⅱ）-PEG NPs.The fabricated PDA-Cu（Ⅱ）-PEG NPs were uniform in shape with a narrow polydispersity.PDA-Cu（Ⅱ）-PEG NPs can enter into tumor cells,and react with glutathione（GSH）to generate Cu（I）,inducing GSH depletion.Meanwhile,the formed Cu（I）could catalyze H₂O₂ to produce hydroxyl radicals via the Fenton-like reaction.Under the irradiation of 808 nm（1 W/cm²）laser,the formed PDA-Cu（Ⅱ）-PEG NPs displayed good photothermal conversion efficiency（33.15%）and photothermal stability.Flow cytometry data showed that PDA-Cu（Ⅱ）-PEG NPs could be effectively internalized by 4T1 cells.Under the near-infrared light irradiation,PDA-Cu（Ⅱ）-PEG NPs can generate hyperthermia and·OH for photothermal/chemodynamic therapy against tumor cells.This multifunctional polydopamine-based nanoplatform provides research basis for the development of photothermal-enhanced chemodynamic therapy against tumor cells.2.Based on the principles of photothermal-enhanced chemodynamic therapy,in this paper,a kind of mesoporous PDA（MPDA）/gold/manganese dioxide（MPDA-Au-Mn O₂）multifunctional nanoplatform was constructed to enhance chemodynamic therapy from multiple angles against tumors and achieve the purpose of efficient antitumor.Firstly,MPDA was prepared,followed by Au NPs loading and Mn O₂ shell coating in situ,finally forming MPDA-Au-Mn O₂NPs.When MPDA-Au-Mn O₂NPs internalized into tumor cells,the Mn O₂ shell was gradually degraded by GSH,releasing Mn²⁺and exposing Au/MPDA NPs.Mn²⁺could generate·OH through the Fenton-like reaction with the existence of HCO₃^-in the acidic tumor microenvironment.Au NPs can deplete GSH by Au-S bonds interaction.MPDA can act as photothermal agents for photothermal therapy.The reducibility of MPDA was compromised during the preparation process,decreasing the clearance of·OH and enhancing the efficacy of CDT.MPDA-Au-Mn O₂NPs showed good photothermal stability and high photothermal conversion efficiency（32.9%）under NIR-I laser irradiation（808 nm,1 W/cm²）.In vitro and in vivo experimental data displayed that this nanocomposite had good biocompatibility and an excellent antitumor effect.This multifunctional nanoplatform based on mesoporous polydopamine provides a reference for the development of multimodal tumor therapy strategies.