Preparation And Properties Of Composite Nanodrugs Based On Enhanced Chemodynamic Therapy

Cancer has become the leading cause of disease death worldwide.The development of early diagnosis and treatment of cancer is the key to guarantee people's public health.Chemodynamic therapy?CDT?is defined as in situ therapy that uses the Fenton response or Fenton-like response to generate·OH at the tumor site.In short,iron-based nanomaterials dissolve ferrous ions under the mildly acidic conditions of TME,triggering the Fenton reaction to produce H₂O₂ excessively,generating·OH,thereby triggering apoptosis and inhibiting tumor growth.Most importantly,this method guarantees normal tissue safety to a certain extent,because in a normal microenvironment,the Fenton reaction is greatly suppressed under weak alkaline conditions and under H₂O₂ deficiency.Nevertheless,the potential toxicity of nanomaterials needs further consideration.This strategy not only broadens the application of Fenton response,but also demonstrates its potential for clinical transformation.Compared with chemotherapy,radiotherapy,photothermal therapy,and photodynamic therapy,CDT has the following advantages:1)strong selectivity,and 2)can be activated by endogenous stimuli.At the same time,we also learn from some drugs,because their principle of treatment is based on Fenton or Fenton-like response.Therefore,further research on CDT has attracted widespread attention in the field of tumor treatment.Based on the above research background,this thesis develops nanomaterials using liposomes as a carrier and combined with other therapies to enhance CDT.The antitumor effect of the nanomaterials is studied,and the sites where the drugs reach by MRI and the effect of tumor treatment is monitored in real time.The main research contents are as follows:We designed and developed a biocompatible nanosystem,which self-assembled soybean lecithin,paclitaxel,MnO₂ nanoparticles and glucose oxidase?GOx?into PTX/MnO₂/GOx-Lips,and then modified hyaluronic acid on the surface of the nano system?HA?to enhance tumor targeting.Mn O₂ consumes endogenous GSH to produce Mn²⁺,which reduces the elimination of·OH and enhances the CDT effect.At the same time,Mn²⁺-mediated magnetic resonance imaging?MRI?can also synchronously monitor the therapeutic trajectory of nanosystem in vivo.In addition,O₂ produced during the CDT process promotes starvation-like treatment,thereby providing more H₂O₂ for CDT enhancement.Therefore,our design solves the long-standing limitations of CDT,shows good antitumor efficacy,and also achieves efficient synergy of CDT,hunger-like treatment,chemotherapy and real-time tracking.The system also showed good antitumor effects,with a cell survival rate of only 10.44%.In vivo antitumor experiments in mice showed that the volume of the PTX/MnO₂/GOx-Lip-HAs group was reduced to about 58.12 mm³compared with the tumor volume of the saline group?953.25 mm³?,confirming that the PTX/MnO₂/GOx-Lip-HAs nanoparticles'dual catalyst and PTX treatment system can most effectively suppress tumors.And through serum indicators and?H&E?staining analysis,it was confirmed that the nanocarrier has no toxic side effects on the body and has good biological safety.In addition,we propose an intelligent,sequential function nano-platform for therapeutic diagnostics,which effectively inhibits tumor growth through tumor microenvironment response to catalytic response and tumor-specific targeting.We designed a nanostructure of PTX and Co elemental liposomes modified with magnetic Fe₃O₄?PTX/Co-Lips@Fe₃O₄?.First,under the magnetic targeting of Fe₃O₄ after intravenous injection,after endocytosis of tumor cells,Fe₃O₄ can consume GSH overexpressed in the tumor microenvironment,generate Fe²⁺and Fe³⁺with CDT function,and release PTX.Then Fe³⁺and elemental Co react to generate Fe²⁺and Co²⁺with high catalytic capacity,and further catalyze more H₂O₂ through Fenton reaction to complete CDT enhancement.In the end,T₁/T₂ weighted dual-modality MRI-guided chemotherapy and CDT enhancement produced a large amount of highly toxic·OH,leading to apoptosis and death of tumor cells,and effectively killing cancer cells.In vivo anti-tumor experiments show that the PTX/Co-Lips@Fe₃O₄+MG group also has excellent therapeutic effects,and shows good clinical transformation potential in the field of cancer treatment.