Preparation And Characterization Of Novel Drug Delivery System Based On Prussian Blue Nanoparticles For Photothermal Therapy And Chemotherapy

Photothermal therapy(PTT)is a thriving,non-invasive cancer therapy stratagy.The mechanism of PTT is based on hyperthermia therapeutic as cancer cells would be killed at overhigh temperature.Heating capacity of photothermal agents determined treatment effect.Owing to the fact that single cancer treatment stratagies are useless to tenacious cancer cells,so researchers have started to investigate multi-therapy combination,such as chemotherapy,immunotherapy,radiotherapy,etc.it is important to develop good biocompatible,combined multi-therapy photothermal agent.The main contents and results of this dissertation in three parts as blew:In this research,inspired by good photothermal conversion efficiency of prussian blue,we proposed a facile two-step strategy to modify the surfaces of hydrophobic PB NPs.Hydrophobic doxorubicin(DOX)was used as a model anticancer drug and encapsulated into hydrophobic lipid region of PEGylated PB NPs formed by DSPE-PEG2000 and oleyla mine,PEGylated PB-DOX NPs would show synergistic cancer ablation effects,useful for combinational photothermal-chemo treatment of cancer cells.Prussian blue has preformed extraordinary photothermal conversion and good biocompatibility in last chapter,we further synthesized hollow mesoporous prussian blue nanoparticles(HMPBs)for enhancing drug loaded capacity.For the purpose of overco ming drug resistance during chemotherapy period,we utilized tetradecanol as a mediation to co-load two different kind of anti-cancer drugs.Tetradecanol is a special phase change material which has a suitable melting point(38oC)that slightly higer than normal body temperature.As a result,we could achieve “zero release” when nanoparticles are doing long circulation in vivo.In addition,benefiting from the phenomenon that generated heat could improve drug cellular uptake by increasing the cellular metabolism and membrane fluidity,the as-prepared(PCM+drugs)@HMPBs also showed a significant synergistic cell-killing effect from combination chemotherapy.After previously studied,we would like to develop more efficiency combination stratagies.So we added autophagy into photothermal therapy.CQ as a autophagy inhibitor is able to influence cell's normal function,destroy cellular self-repair,so cells survived from hyperthermia will finally go apoptosis.We evaluated photothermal capacity of HMPBs@PCM,and then synergetic therapeutic effect.