Nano-calcium Phosphate Drugs Based On Supramolecular Chemistry Of Cyclodextrin For Lung Cancer A549 Cells Treatment

Lung cancer was the leading cause for cancer death among the malignant cancer.Currently,clinical lung cancer treatment are mainly chemotherapy,radiotherapy,molecular targeted therapy and surgery.As one of the important clinical treatment,chemotherapy has a serious side effects during the cure prograss,such as,poor tumor selectivity,serious side effects and so on.So we have developed an efficient and low-toxicity chemotherapy mothod for lung cancer treatment.We developed a biocompatibility nano-drug delivery systems to transport the hydrophilic or hydrophobic small molecule drugs.This carrier can effective encapsulated the cargos and accumulated in the tumor tissue by the EPR(Enhanced Permeability and Retention)effect with releasing drug at tumor acid environment and killing cancer cells quickly.This nano-drug delivery system has the potential to improve the diagnostic accuracy and obtain an effect chemotherapy for lung cancer.This dissertation can be categorized into two main parts as described below:We developed a nano-calcium phosphate drugs based on supramolecular chemistry of cyclodextrin to transport the hydrophilic imaging small molecules Rhodamine B or hydrophobic small molecule drugs Docetaxels for lung cancer A549 cells treatment.1.Successfully synthesized carboxymethylated β-cyclodextrin,and help build calcium phosphate nano-drug delivery system.First,we successfully synthesized the carboxymethyl β-cyclodextrin(CM-β-CD)and afford the functions of encapsulating cargo molecules(RBs or Dtxls)formed nano-calcium phosphate drugs(describe as RBs-en-CPNPs or Dtxls-en-CPNPs).We quantitatively analyzed RBs and Dtxls drugs content by UV spectrophotometer and high performance liquid chromatograph and studied the influence of CM-β-CD for thestructure of nano-calcium phosphate drugs.Since the morphology of RBs-en-CPNPs or Dtxl-en-CPNPs was uniform and stable in the internal environment,we use PBS buffer at p H 7.4 and p H 5.4 simulated the extracellular and intracellular environment respectively and the release behavior of RBs-en-CPNPs or Dtxl-en-CPNPs was studied.As a result,the drug can release quickly from the nano-calcium phosphate at the weak acid environment.Nevertheless,no drugs release at the neutral environment,demonstrating such a nano-calcium phosphate drugs can avoid the side effect during the transportation.2.To construct human lung cancer A549 cell model and study the uptake behavior and the killing effect of A549 cells based on nano-calcium phosphate drugs.We selected human lung adenocarcinoma A549 cell line as a model to examine the cytotoxicity of nano-calcium phosphate drugs(Dtxls-en-CPNPs).Due to the lack of fluorescence of Dtxls,the uptake behavior of Dtxls-en-CPNPs is hard to detect at the biological level.So we choose rhodamine B as a fluorescence probe to study the uptake behavior of nano-calcium phosphate drugs(Dtxls-en-CPNPs).The results of flow cytometry(FACS)and confocal laser scanning microscopy(CLSM)showed the red fluorescence getting stronger and stronger with the culture time prolong,demonstrating the RBs-en-CPNPs degraded at the acid environment(p H=4.5~5.5)and release the RBs quickly.In addition,we also examined the cytotoxicity of Dtxls-en-CPNPs on A45 cells by MTT assay,which proved the nano-calcium phosphate drugs(Dtxls-en-CPNPs)can delivery small molecule chemotherapeutic drugs effectively for lung cancer treatment.In conclusion,we successfully prepared a p H-responsive nano-cacium phosphate drugs(RBs-en-CPNPs and Dtxls-en-CPNPs)based on supramolecular chemistry of cyclodextrin for lung cancer treatment.Such a nanomedicine can release drug quickly at the tumor microenvironment,improve the selectivity of chemotherapy drug and reduce the side effects of chemotherapy.Therefore,the calcium phosphate nanomedicine provides a potential strategy for the chemotherapy and treatment of clinical lung cancer.