The Study On Mesoporous Titanium Dioxide Based Nano-drug Delivery Systems For Chemotherapy In Combination With Photodynamic Therapy

Malignant tumors are major diseases that threaten the health of human beings.At present,there are two main treatment methods for malignant tumors:chemotherapy and radiotherapy.Although these two methods can inhibit tumors to some extent,their applications of chemotherapy and radiotherapy have limitations due to their lack of specificity and poor prognosis.Photodynamic therapy?PDT?is an oxygen-dependent photo-triggered,non-invasive treatment that shows its unique advantages in cancer treatment.For effective PDT,a nanoscale carrier is typically required to achieve tumor targeted delivery of the photosensitizer.Mesoporous titanium dioxide nanoparticles?MTN?is a widely studied nanomaterial that has been studied for drug delivery systems due to its low cytotoxicity,suitable drug-loaded pore size,and pore structure.At the same time,mesoporous titanium dioxide nanoparticles can also be used as photosensitizers for PDT.This thesis is divided into two parts.In the first part,hyaluronic acid?HA?and ADH-1?a cyclic pentapeptide?modified mesoporous titanium dioxide nano drug delivery system?ADH-1-HA-MTN?was prepared.DOX was used as a model drug to conduct anti-drug resistance studies against tumor EMT cells.The non-small cell lung cancer cell line A549 was induced by transforming growth factor TGF-?₁ to establish the EMT cell model?A549/EMT?.On this basis,the safety,cell targeting,reactive oxygen species?ROS?production,PDT therapeutic effect and the cytotoxic effect of the constructed nanocarriers were investigated.Further,the anti-drug resistance mechanism of ADH-1-HA-MTN on A549/EMT cells was studied.The results showed that ADH-1-HA-MTN had a good targeted delivery ability to A549/EMT cells,and could produce reactive oxygen species under X-ray irradiation.Combined with the chemotherapy effect of DOX,it could effectively kill A549/EMT cells.Western blotting experiments showed that ADH-1-HA-MTN overcame tumor drug resistance by inhibiting the expression of N-cadherin and blocking EMT process.In the second part of this paper,based on the photodynamic properties of mesoporous titania,it was further oxidized to obtain mesoporous peroxide nanoparticles?TiO_x?.The YSA peptide and polyethylene glycol?PEG?were modified on the surface of TiO_x to construct a tumor-targeted nano drug delivery system?YSA-PEG-TiO_x?with enhanced photodynamic effects.In this part,Cantharidin?CTD?was used as a model drug,and A549 cells were selected as the research object.The safety and cell targeting of the nanocarriers were investigated.ROS production and PDT therapeutic effect of TiO_x and MTN were compared.The results showed that YSA-PEG-TiO_x could target to A549 cells.The strong PDT treatment effect combined with CTD can significantly improved the cytotoxicity to A549cells.In summary,the tumor-targeted drug delivery systems based on mesoporous titania nanocarriers could achieve the combined effect of chemotherapy and PDT to kill tumor cells.