Preparation And Characterization Of Nanodrugs Based On Fe³⁺-tannic Acid Network Structure

In recent years,metal-polyphenol networks（MPN）have been generally used in the field of nano-drug delivery due to their p H-responsiveness.Based on this network,a variety of anti-tumor drugs can be co-loaded,and numerous tumor therapy methods can be synergistic to improve the effect of inhibiting tumor proliferation.In addition,since both Ferroptosis（FPT）and photodynamic therapy（PDT）are correlated with the concentration of reactive oxygen species（ROS）in tumor cells,this paper proposes the use of MPN as a carrier platform to synergize this two anti-tumor methods,which will effectively alleviate the reduced efficacy of PDT due to hypoxia within the tumor.The controlled release of loaded drugs is also realized through the p H responsiveness of MPN,which in order to achieve the proliferation of tumor cells with more excellent inhibition effect.In this study,tannic acid（TA）and Fe³⁺self-assembled iron-tannic acid（Fe^ⅢTA）network structure was designed as a nanocarrier,at the same time loaded with FPT inducer Sorafenib（SRF）and photosensitizer Protoporphyrin D1sodium（NAPP）.The nanoparticle aggregates at the tumor cells due to Enhanced Permeability and Retention（EPR）effect.After endocytosis into the cells,the p H responsiveness of the Fe^ⅢTA network structure is stimulated by the change of intracellular p H,which leads to its lysis.Releasing the loaded drugs SRF and NAPP to induce the occurrence of FPT and PDT.At the same time,the Fe³⁺released is reduced to Fe²⁺under the action of TA.Fe²⁺promotes the Fenton reaction and produces a large amount of ROS,which further strengthens the inhibitory effect of FPT on tumor cells.The experimental results show that the average particle size of SRF@Fe^ⅢTA and SRF@Fe^ⅢTA-NAPP nanoparticles is 191.3 nm and 276.5 nm,respectively,and they are all regular spheres by observing the SEM.The molar ratio of each component of nanodrug was Fe³⁺:TA:NAPP:SRF=1:1.52:2.39:10.39;In the simulated in vitro drug release experiments,the nano-drug was p H-responsive and could achieve specific release,the cumulative release amount reached about 38%within 72h was 19 times higher than in the high p H group.In vitro MTT cytotoxicity assay,the inhibition of tumor cell growth of nanoparticles loaded with two drugs was much higher than that of two drugs of the same concentration alone,indicating the advantage of combined therapy.In the in vitro cell uptake experiment,with the increase of the concentration,the intracellular drug concentration stabilized at 5～6μM,the maximum uptake rate reached 88.19%.In the time-dependent uptake experiment,the cell uptake rate was stable at about 75%within 72 h,the drug availability was high.Through the comparison of cell survival rate after incubation with Ferroptosis inhibitor and nanodrugs alone,the design idea of nanodrugs inducing and promoting iron death in tumor cells was verified.The MPN combined with FPT and PDT,significantly enhanced the growth inhibition of tumor cells.This strategy also provides a new idea for the design and development of anti-tumor nanomedicines.