Application Of Functionalized Hollow Mesoporous MnO₂ Nanospheres In Collaborative Diagnosis And Treatment Of Cancer

The rapid reproduction and easy metastasis of malignant solid tumors make them the top killer of human health.Compared with traditional chemotherapy,phototherapy has more significant efficacy and fewer side effects.Nanomedicine carriers have been widely used in the delivery of anticancer drugs because of their high drug delivery capacity and their ability to increase drug circulation time and retention in tumor areas.Hollow mesoporous MnO₂has a high capacity forfat-solublee small molecule anticancer drug delivery,so it is of great research value to use hollow mesoporous MnO₂in cancer treatment.In the first protocol of this paper,we used unusual photodynamic therapy to inhibit the growth of solid tumors and achieved good therapeutic results in animal and cell experiments.Traditional photodynamic therapy requires the interaction of photosensitizer and excitation light source,but the application and development of photodynamic therapy have been greatly hindered due to the limited penetration of external light source and insufficient uptake of photosensitizer by cancer cells In this paper,a new type of nanoreactor containing（HMPP-Ce6＆CPPO-GOx,HMPP-C＆C-GOx）photosensitizer chlorin E6（Ce6）and bis（2,4,5-trichloro-6-carbopentoxyphenyl）oxalate（CPPO）was proposed by using hollow mesoporous manganese dioxide nanospheres（Hollow MnO₂,HMnO₂）coated with glucose oxidase（GOx）.CPPO provided chemical power for the production of reactive oxygen species（ROS）in Ce6.CPPO make ROS generation no longer dependent on the external light source,and the scheme in this paper could solve the problem of insufficient penetration of external light source to biological tissues to a first degree.Furthermore,the large drug loading capacity of hollow mesoporous MnO₂solved the problem that photosensitizer is difficult to accumulate the netumors lid tumor.When the cells ingested drugs,glucose generated a large amount of hydrogen peroxide（H₂O₂）under the catalysis of GOx.H₂O₂not only promoted the disintegration of the manganese dioxide shell to release drugs,but also produced oxygen to improve the tumor microenvironment.It also activated CPPO and transfered energy to Ce6 to convert O₂into ROS and order cancer cell death in addition to starvation therapy with glucose oxidase.In cell experiments,the semi-lethality and total lethality of A549 cells could be achieved after incubation with HMPP-C＆C-GOx at a concentration of 10μg/mL for 4 h and6 h.In vivo experiments,tumor-bearing mice were treated with a drug concentration of 1.5mg/mL（calculated according to the concentration of MnO₂）.At the end of the treatment period,the tumor size of the mice in the different groups was more than 10 times that of the blank control group.Subsequently,Tunel method was used for immunofluorescence staining and photographing of mouse tumor tissues.Different colors of blank control group and experimental group demonstrated different killing effects of different drugs on mouse tumor cells.The tumor tissue treated with HMPP-C＆C-GOx showed a large area of tumor tissue apoptosis.In the second scheme,we still used phototherapy as the main treatment for cancer.In recent years,AIE（Aggregation-Induced Emission）molecules with aggregation-induced luminescence have made a big splash in the field of cancer treatment.However,how to deliver a large amount of AIE drugs to the cancer area in the treatment process is still a major research focus.Hollow mesoporous MnO₂was used as a drug transport carrier due to its high efficiency of drug loading.After loading a large number of AIE drugs with photothermal properties and Hsp 90 protein inhibitor Hsp 990,the drug was encapsulated with cancer cell membrane to obtain a nano"train"that can use cancer cell membrane for homologous targeting and load a large number of drugs（HMP-A＆H-M）.After the drug is ingested by the cancer cell membrane,due to the effect of reduced glutathione（GSH）and excessive H₂O₂in the cancer cell,the hollow mesoporous manganese dioxide shell is broken to release AIE molecule and Hsp 90 protein inhibitor.When AIE drugs were irradiated with a laser,AIE drugs accumulate and produce heat.In addition,the inhibition of Hsp 90 protein activity increases the sensitivity of cancer cells to heat,leading to cancer cell death.I also achieved excellent photothermal effects in the subsequent in vitro characterization of drugs and cell experiments.In vitro validation of drug properties showed that the drug loading of hollow mesoporous HMnO₂to the AIE molecule used was up to 82%.In vitro drug performance experiments and in cell photothermal performance experiments show that the temperature can be raised about 25℃after 5 min laser irradiation,which is enough for photothermal therapy for cancer treatment.