Study On Drug Delivery System Based On Near-infrared Response And Fenton Reaction For Combined Anti-tumors

Nowadays,chemotherapy is still the most commonly used treatment method because it has a high therapeutic effect on primary（metastatic）tumors.Although the therapeutic effect of small molecule anti-tumor drugs is better,the practical application of this method has certain limitations,such as poor tumor selectivity and drug resistance.The establishment of nano-drug delivery system can achieve precise and effective drug delivery,and presents the advantages of small side effects,high biocompatibility,and good bioavailability.Secondly,single chemotherapy limits the therapeutic effect of drug-resistant tumors.Multifunctional nanomaterials with two or more treatment methods are designed for co-assembly and co-delivery of drugs to achieve the combination of multiple modes of diagnosis and treatment.Both clinical practice and exploratory research have shown that a single treatment plan can not completely eradicate tumors,and it is also weak in preventing tumor metastasis.Therefore,it is very valuable to design and synthesize new nano-drug delivery materials with multimodal therapy.In this paper,manganese dioxide（Mn O₂）is mainly used as the fenton reactant to encapsulate anti-tumor drugs into nano-materials.Realizing the expectation of multi-modal therapy for tumor treatment.We have designed and synthesized a new type of yolk shell structured nanoparticles（HMCMD-PEG）for combined tumor treatment of photothermal therapy（PTT）,chemotherapy and chemokinetic therapy（CDT）.In brief,the Mn O₂ core was formed in situ in the cavity of mesoporous copper sulfide（HMCu S）,and doxorubicin（DOX）is loaded through the mesopore and transported to the tumor site.,The temperature of the HMCMD-PEG aqueous solution can be from 1.83°C to 51.34°C under near-infrared light irradiation,it has a good photothermal conversion efficiency to realize PTT.Mn O₂reacts with glutathione（GSH）overexpressed in cancer cells to generate Mn²⁺,which catalyzes endogenous hydrogen peroxide（H₂O₂）in tumor cells to produce highly toxic reactive oxygen species（ROS）through this fenton-like reaction to achieve CDT under NIR.The CDT effect is significantly enhanced.Cell experiments showed that after cells ingested HMCMD-PEG nanomaterials under near-infrared light irradiation,the growth inhibition rate of breast cancer cells（MCF-7）was as high as 92.18%,and the apoptosis rate was 71.24%.In addition,we have also built a dual cascade catalytic nanoplatform（PBMO-GH）based on the consumption of GSH,cascade-enhanced CDT and photothermal conversion to achieve the multi-modal therapeutic effect of the combined treatment of PTT,CDT and starvation therapy（ST）.Mn O₂depletes GSH in cancer cells,relieves the inhibitory effect of high concentrations of GSH on ROS generation,and enhances the fenton-like response mediated by Mn²⁺.On the other hand,Prussian blue decomposes H₂O₂ to produce oxygen,which increases the oxygen content in tumor cells.Glucose oxidase（GOD）catalyzes the consumption of glucose,achieving the effect of ST.The temperature can rise to 48.9°C under NIR(808 nm,1.0 W cm^-2),which has a good PTT effect.Cell experiments and mice experiments have verified that the nano-platform has a good anti-tumor effect.