Hollow Manganese Silicate Materials For Cancer Cell Diagnosis And Therapy

Chemodynamic therapy（CDT）is an emerging cancer treatment method based on the tumor microenvironment（TME）.CDT uses excess H₂O₂in the TME as a reactant,transition metal ions(such as Fe^2+/3+,Mo^4+/6+,Mn^2+/4+,Cu^+/2+,etc.)as a catalyst to induce Fenton or Fenton-like reactions to generate reactive oxygen species（ROS）and induce tumor cell apoptosis,but its limited endogenous H₂O₂content weakens its anticancer effect.Moreover,glutathione（GSH）is highly expressed in cancer cells.It acts as an essential antioxidant and free radical scavenger in the body,which can scavenge reactive oxygen species and further weaken the treatment effect.In this study,hollow manganese silicate nanoparticles（MSNs）were prepared,loaded with the anticancer drug doxorubicin（DOX）,which was catalyzed by a TME-responsive cascade to realize magnetic resonance imaging（MRI）-mediated diagnosis and therapy of cancer cells.MSNs were degraded in response to the acidic and GSH conditions of tumors,and the high-valence manganese in MSNs undergoes redox reactions to consume GSH and release DOX and Mn²⁺.Mn²⁺not only acts as an MRI contrast agent but also catalyzes the conversion of endogenous H₂O₂into hydroxyl radicals（·OH）for CDT.By characterizing and analyzing the microscopic morphology,chemical composition and surface potential of MSNs,the ability of MSNs to catalyze H₂O₂to generate ROS and consume GSH was explored,and the in vitro MRI test was performed to simulate the tumor microenvironment.The inhibitory effects on the migration,invasion and growth of cancer cells were studied by cytotoxicity experiments,transwell experiments and tumor spheroids experiments.The specific work content is as follows:1.Using SiO₂nanoparticles（～28 nm）as the silicon source and template,about10 nm manganese silicate nanoparticles（MSNs）were formed through the"SiO₂sacrifice and in situ silicate growth"method,loaded with anticancer drugs DOX,the drug loading was 256 mg g^–1.2.To explore the chemodynamic activity of MSNs,methylene blue（MB）was used as an indicator for the generation of·OH,5,5’-Dithiobis（2-nitrobenzoic acid）（DTNB）was used as an indicator to investigate the GSH consumption capacity of MSNs;the effect of MRI and the drug release behavior were explored by simulating the TME of tumor cells.3.The possibility of DOX loaded by manganese silicate（MSNs/DOX）into cells was verified by the uptake experiments of DOX by MDA-MB-231 cells,the cytotoxicity of MSNs and MSNs/DOX was evaluated by the SRB method,the way of MSNs/DOX-induced breast cancer death was verified by apoptosis measurement,the inhibitory effect of MSNs/DOX on the migration and invasion abilities of MDA-MB-231 cells was investigated by cell wound-healing and transwell experiments and the growth inhibitory effect of MSNs/DOX on MDA-MB-231 cells was evaluated by tumor spheroids assay.The MSNs/DOX prepared in this study can significantly inhibit the invasion,migration and growth of MDA-MB-231 cells,and have certain application prospects in the field of cancer diagnosis and therapy.