Construction And Properties Study Of Antitumor Nanosystem Based On Mesoporous Polydopamine

In recent years,the incidence and mortality rates of cancer have increased rapidly.Therefore,it is particularly important to develop new materials and therapies to overcome drug resistance and improve the effectiveness of tumor treatment.With the continuous development of nanotechnology in the biomedical field,its use for multimodal combination therapy has become a research hotspot.In this paper,a series of multimodal antitumor nanosystems were constructed based on mesoporous polydopamine（MPDA）with excellent biocompatibility and easy modification.Their structures and properties have been more systematically characterized and investigated.The specific research contents are as follows:1.Firstly,submicron SiO₂ nanoparticles were prepared by sol-gel method,Pluronic F127 and1,3,5-trimethylbenzene（TMB）were then used as organic templates,and polydopamine（PDA）layer was constructed on the surface of Si O₂ nanoparticles using alkaline self-polymerization reaction.Then the template was washed away by solvent,and the MPDA layer with mesoporous structure was obtained.The Si O₂ particles were etched off using Na OH solution to obtain hollow mesoporous polydopamine（HMPDA）microcapsules.Finally,gold nanoparticles（Au NPs）were deposited in situ onto the HMPDA microcapsules using trisodium citrate solution to obtain HMPDA@Au NPs microcapsules.The adsorption performance and adsorption mechanism of the above microcapsules on dye molecules were investigated using the organic dyes rhodamine B（Rh B）and methylene blue（MB）as target molecules.The loading and sustained release properties of microcapsules were investigated using doxorubicin hydrochloride（DOX）as a target drug.The photothermal performance of the microcapsules were also studied.The results showed that the HMPDA@Au NPs microcapsules had high photothermal conversion efficiency,with an average DOX loading capacity（334.78 mg/g within 24 h）,and the release rate was about 44.8%under photothermal conditions within 8 h.In vitro cellular experiments showed that this nanosystem,which integrated chemotherapy（CT）and photothermal therapy（PTT）,had a significant inhibitory effect on A549 tumor cells under the combined effect of near light and drugs（survival rate of 23.67%）.2.A nucleus-satellite nanosystem with Fe₃O₄ nanoparticles as the core,HMPDA as the shell layer,dendritic macromolecule-gold nanoparticles（G5-Au）as the small satellites,and DOX as the loaded drug was designed and constructed.The anti-cancer drug DOX could be loaded in the cavity structure of HMPDA layer and G5-Au nanoparticles.Thus,the drug loading capacity of the system was relatively large.In addition,the prepared Fe₃O₄@HMPDA@G5-Au nanosystem had good photothermal properties,because PDA and Au NPs were both good photothermal agents.Combination of PTT and drug therapy could significantly enhance the ablation of tumor cells with minor side effects.The decomposition of H₂O₂ in the tumor site catalyzed by the Au NPs with catalase-like activity could also produce oxygen to alleviate tumor hypoxia.In addition,because of the magnetic properties of Fe₃O₄ nanoparticles,the Fe₃O₄@HMPDA@G5-Au nano drug delivery carriers also had magnetic targeting performance and could reach the specified position under the guidance of external magnetic field.The results showed that the average DOX loaded amount of the prepared carriers was 473.83 mg/g,the DOX release rate in 24 h could achieve 61.3%under the synergistic effect of p H acidic environment and NIR conditions.The cytotoxicity assay showed that the nanosystem had a significant inhibitory effect on Hep G2 cells.The Fe₃O₄@HMPDA@G5-Au nucleus-satellite nanotherapy system prepared in this chapter effectively improved the dilemma faced by conventional therapy through strategies such as PTT,CT,relief of hypoxia,cascade delivery,magnetic targeting and p H-responsive drug release,and had a greater application in the precision deep treatment of tumors.3.The Fe₃O₄nanoparticles were prepared as nuclei by the solvothermal method,and the drug carriers with MPDA layer as the shell layer were prepared by the self-assembly method（Pluronic F127 and TMB were used as templating agents to obtain mesopores,and the templating agents were washed away by solvent）.Subsequently,Au nanoparticles were modified on the MPDA layer by in-situ deposition method;and MB fluorescent dyes were adsorbed on the MPDA surface,then the anti-cancer drug DOX was loaded.The above composite particles were coated with bovine serum protein（BSA）to obtain the Fe₃O₄@MPDA@Au/MB/DOX@BSA treatment integrated anti-tumor nanosystem.The adsorption and fluorescence properties of MB dyes,the loading and release properties of DOX,the photothermal properties and the in vitro cytotoxicity of the nanosystem were investigated.The results showed that the Fe₃O₄@MPDA@Au/MB/DOX@BSA nanosystem has high photothermal conversion efficiency,good fluorescence signal,low toxicity to normal cells,and significant inhibition of tumor cells（survival rate of 22.12%）.The average DOX loading of the nanoparticles was 96.26 mg/g within 24 h,and the release rate was about 50.9%under acid and NIR conditions within 8 h.The composite material prepared in this chapter assembles components with tumor diagnostic and therapeutic functions in one nanosystem,which was expected to achieve early diagnosis,targeted localization and precise treatment of tumors.4.A natural glucose oxidase（Gox）was integrated with hollow mesoporous manganese dioxide nanoparticles（H-Mn O₂）to construct a biorecycling reactor.The photosensitizer IR780was infiltrated into the hollow cavity through the pores of H-Mn O₂ nanoparticles,and then a layer of MPDA was wrapped on the H-Mn O₂ nanoparticles.Photothermal treatment of tumor cells induced by IR780 and MPDA,heated by an external light source,generates heat that could be used to accelerate Fenton catalysis.Finally,grafted iron phosphate particles（Fe Pi）act as efficient Fenton’s reagent to accelerate the Fe³⁺/Fe²⁺cycle to ensure Fe²⁺supply under the reductive effect of dopamine,and the generated Fe²⁺reacted with H₂O₂ to produce highly toxic·OH to kill cancer cells.Photothermal experiments showed that the H-Mn O₂@Gox/IR780@MPDA@Fe Pi（HMGIMF）nanosystem had high photothermal conversion efficiency,which was applied to photothermal therapy.The nanosystem combined oxygen production,ST,PTT and CDT,and the multiple therapies promoted each other,providing a way to improve tumor efficacy.The in vitro cytotoxicity assay evaluated the effect of the nanosystem on HL-7702 and 4T1 cells,the results showed that the HMGIMF multifunctional nanosystem had a significant inhibitory effect on 4T1 cells（13.21%survival rate）,while no significant inhibitory effect on HL-7702 cells.