| BackgroundPrimary liver cancer is one of the most deadly malignant tumors in the world,and the incidence rate is high every year.Treatment options for advanced liver cancer are limited and the prognosis is very poor,so there is an urgent need to develop new and effective treatments.Photothermal therapy involves shining a laser at a site rich in photothermal conversion reagents to convert light energy into heat energy,denaturating heat-resistant proteins and ultimately killing cells.Quantum dots(QDS)are a kind of nanomaterials with excellent physical and chemical properties,which can be enriched in tumor sites when combined with targeted molecules.And has a strong photothermal conversion performance.Black phosphorus QDS are a new type of semiconductor nanomaterial with two-dimensional lamellability.Besides excellent photothermal conversion performance,they can also generate reactive oxygen species such as superoxide anions and hydroxyl radicals,which can kill tumor cells.OXA liplatin is the third generation of platinum derivatives,which is one of the first-line drugs in the comprehensive treatment of various cancers,including liver cancer.Drug liposomes are microvesicles encapsulated by lipid bilayer,which have the functions of slow release,targeting,reducing toxicity and improving stability.MethodsSilver doped black phosphorus QDs and OXA liplatin liposomes were prepared,and black phosphate-OXA liplatin liposomes were synthesized and characterized.Fifteen 6-week-old male BALB/C nude mice were established subcutaneous transplantation tumor model of human hepatocellular carcinoma cells in nude mice,and were randomly divided into blank control group,OXA liplatin treatment group,OXA liplatin liposome treatment group,and black phospho-OXA liplatin liposome non-light/photothermal treatment group(5 groups,3 in each group).Each group was injected every 2 days through the tail vein.In the photothermal treatment group,the tumor site was irradiated with near-infrared light for 5min after 6h of injection,and the tumor volume was measured and recorded every 2 days to draw the growth curve.On the 15th day,the mice were sacrificed,the tumors were stripped and weighed,and the inhibitory rate was calculated.The tumors and major organs(heart,liver,spleen,lung and kidney)were taken for HE staining observation.The expressions of Ki 67 and Caspase 3 were detected by immunohistochemistry in the tumor tissues.ResultsThe corresponding QDs were synthesized by characterization experiments.Black phospho-OXA liplatin liposome photothermal treatment group showed the most obvious antitumor effect,followed by OXA liplatin treatment group,OXA liplatin liposome treatment group and non-photothermal treatment group.HE staining of organ sections showed that the drug form of black phospho-OXA liplatin liposome had minimal organotoxicity,OXA liplatin liposome had liver and spleen toxicity,OXA liplatin had liver,spleen and kidney toxicity.HE staining of tumor tissue sections and immunohistochemistry of Caspase 3 showed that tumor necrosis and apoptosis were the most obvious in photothermal treatment group,followed by non-photothermal treatment group,OXA liplatin group and OXA liplatin liposome group.Immunohistochemistry showed that Ki 67 was strongly positive in photothermal treatment group,positive in non-photothermal treatment group,and weakly positive in OXA liplatin group,OXA liplatin liposome group and blank control group.ConclusionBlack phospho-OXA liplatin liposomes can play the role of photothermal therapy under near-infrared light,and effectively inhibit the growth of liver cancer by promoting tumor necrosis and apoptosis,but the effect of tumor inhibition is relatively slow under the condition of no light.And has no toxic effect on the heart,liver,spleen,lung and kidney and other important organs.OXA liplatin and OXA liplatin liposome have similar antitumor effects on subcutaneous tumor of hepatocellular carcinoma,and have certain organotoxicity. |
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