【摘 要】
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Objective:Bufalin is an effective drug for the treatment of liver cancer.But its high toxicity,poor water-solubility,fast metabolism and short elimination half-life limit its use in tumor treatment.How to make the drug accumulate in the tumor and reduce s
【机 构】
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Department of Traditional Chinese Medicine,Changhai Hospital,Naval Medical University,Shanghai 20043
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Objective:Bufalin is an effective drug for the treatment of liver cancer.But its high toxicity,poor water-solubility,fast metabolism and short elimination half-life limit its use in tumor treatment.How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent prob-lems to be solved.The goal of this study is to solve these problems.Methods:A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized.The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF)were synthesized by copolymer self-assembly in an aqueous solution.The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy.Then,its temperature sensitivity,serum stability,critical micelle concentration (CMC),entrapment efficiency (EE),drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated.Next,the effects of DTIs-BF on cellular uptake,cytotoxicity,and tumor cell inhibition were evaluated.Finally,the accumulation of DTis-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interac-tive video information system.Results:DTIs-BF had a small size,spherical shape,good temperature sensitivity,high serum stability,low CMC,high EE,and slow drug release.The blank BCMs had very low cytotoxicity.Compared with free bufalin,the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced,and the effects were obviously better at 40 ℃ than 37 ℃.In addition,the thera-peutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin.When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer.the accumulation of FITC was significantly increased in tumors.Conclusion:DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.
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