Gold Nanocages For Stimuli-triggered Drug Release And The Applications In Tumor Theranostics

Cancer has become the major threat to human health,but traditional cancer treatments still have big side effects,such as high toxicity,poor targeting and producing multi-drug resistance problem.Therefore,it is urgent to develop effective treatment with low toxicity.The intelligent responsive nanocarriers have the advantages of strong tumor targeting ability,high efficiency and cancer theranostics,which bring new opportunities for the effective treatment of tumors.For example,the gold nanocages?AuNC?were used as drug carriers and diagnostic agents due to theirexcellent biocompatibilityand special optical properties.The temperature-sensitive liposome with the designed phase transition temperature can promote the release of drug under certain temperature.In addition,MnO₂ could be reduced and released oxygen in tumor microenvironment,thus becomes a hot material for tumor targeting oxygenation.In this paper,we has designed and constructed two kinds of nanocarrier systems with different responsive controlled release performance and cancer theranostics.The main research contents as follows:1.Preparation of drug loaded thermosensitive liposomes gold nanocages and its application in drug controlled release and combined treatment of photothermal chemotherapy:The thermo-sensitive liposomes coated and DOX-loaded AuNC?LAD?with uniform size and morphology were prepared by galvanic displacement method,membrane hydration method and ammonium sulfate gradient method.Under the near infrared light?NIR?,LAD had excellent photothermal conversion performance,and it triggered the transformation of temperature sensitive liposomes to release DOX rapidly,with the fluorescence intensity of intracellular DOX increased significantly.This result verified that the NIR could trigger DOX released from the nanoparticles.At the same time,cellular experiments also confirmed that the synergistic treatment of photothermal and chemotherapy could significantly increase the mortality of tumor cells.2.Preparation of the core-shell structure of the AuNC-MnO2?AM?nanoparticles for responsive oxygenation and photodynamic therapy:MnO₂was grown on the surface of Au NC,and coated with polyethylene glycol to increase the stability and biocompatibility of nanoparticles.The quick release oxygen capacity of AM in the acidic hydrogen peroxide solution was detected.In the light of laser irradiation,the nanoparticles in the acidic hydrogen peroxide solution released a large amount of reactive oxygen.Under laser irradiation,a large amount of reactive oxygen species?ROS?was released from nanoparticles in acidic hydrogen peroxide solution,which confirmed that the photodynamic effect of the nanoparticles could be effectively enhanced by the oxygenation.In addition,the experiments showed that nanoparticles had good quantitative optical acoustic imaging and magnetic resonance imaging.In vitro photodynamic therapy experimental results revealed that apoptosis rate of the tumor cells was significantly increased under the NIR,which proved that AM could kill tumor cells efficiently by increasing oxygen photodynamic therapy.In summary,we presented the preparation of two kinds of AuNC for stimuli-triggered drug release and their potential applications in tumor theranostics.Our work may provide experimental guidance and pave the way for the design and synthesis of effective nanotheranostics in future research.