靶向纳米探针在结直肠癌干细胞荧光成像及光热治疗中的研究
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摘要
目的制备CD44v6功能化上转换纳米粒子(UCNPs)探针,用于结直肠癌肿瘤干细胞(CSC)的早期诊断及光热治疗研究。方法采用热解法制备NaYF_4:Yb,Er/Tm纳米粒子,检测其表征及对细胞的毒性;然后与CD44v6抗体耦联,制备成可以检测CD44v6~+细胞的UCNPs探针;用荧光显微镜观察CD44v6UCNPs探针的靶向作用;体外进行CD44v6UCNPs对结直肠癌CSC光热治疗。结果 UCNPs对肿瘤细胞无毒性;成功制备CD44v6UCNPs探针;实现体外结直肠癌CSC的靶向荧光成像和光热治疗。结论成功制备靶向UCNPs探针并将其应用于结直肠癌CSC的荧光成像及光热治疗。
Objective To prepare a functionalized up-conversion nano-probe(UCNPs)of CD44v6 for diagnosis and photothermal therapy of colorectal cancer stem cells.Methods Nanofibers NaYF4:Yb,Er/Tm were prepared by pyrolysis method,and detection of its characterization and toxicity to cells were carried out.Then,UCNPs probes for CD44v6~+cells were prepared by coupling the UCNPs with CD44v6 antibody.Fluorescence microscopy was used to observe the target action of CD44v6 UCNPs.UCNPs were used to photothermal therapy of colorectal cancer stem cells in vitro.Results UCNPs were non-toxic to tumor cells.CD44v6 UCNPs were successfully prepared and targeted fluorescence imaging and photothermal therapy of colorectal cancer stem cells were achieved in vitro.Conclusion The targeted UCNPs were successfully prepared and applied to fluorescence imaging and photothermal therapy of colorectal cancer stem cells.
Objective To prepare a functionalized up-conversion nano-probe(UCNPs)of CD44v6 for diagnosis and photothermal therapy of colorectal cancer stem cells.Methods Nanofibers NaYF4:Yb,Er/Tm were prepared by pyrolysis method,and detection of its characterization and toxicity to cells were carried out.Then,UCNPs probes for CD44v6~+cells were prepared by coupling the UCNPs with CD44v6 antibody.Fluorescence microscopy was used to observe the target action of CD44v6 UCNPs.UCNPs were used to photothermal therapy of colorectal cancer stem cells in vitro.Results UCNPs were non-toxic to tumor cells.CD44v6 UCNPs were successfully prepared and targeted fluorescence imaging and photothermal therapy of colorectal cancer stem cells were achieved in vitro.Conclusion The targeted UCNPs were successfully prepared and applied to fluorescence imaging and photothermal therapy of colorectal cancer stem cells.
引文
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[2]LAPIDOT T,SIRARD C,VORMOOR J,et al.A cell initiating human acute myeloid leukaemia after transplantation into SCID mice[J].Nature,1994,367(6464):645-648.
[3]KENNEDY J A,BARABF,POEPPL A G,et al.Comment on"tumor growth need not be driven by rare cancer stem cells"[J].Science,2007,318(5857):1722-1722.
[4]CLARKE M F,DICK J E,DIRKS P B,et al.Cancer stem cells--perspectives on current status and future directions:AACR Workshop on cancer stem cells[J].Cancer Res,2006,66(19):9339-9344.
[5]CROKER A K,ALLAN A L.Cancer stem cells:implications for the progression and treatment of metastatic disease[J].J Cell Mol Med,2008,12(2):374-390.
[6]CIVENNI G,SOMMER L.Chemokines in neuroectodermal development and their potential implication in cancer stem cell-driven metastasis[J].Semin Cancer Biol,2009,19(2):68-75.
[7]MISRA S,GHATAK S,PATIL N,et al.Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6pathway and inducing cytotoxicity in colon cancer cells[J].Bioorg Med Chem,2013,21(9):2551-2559.
[8]CHEN Z G,CHEN H L,HU H,et al.Versatile synthesis strategy for carboxylic acid-functionalized upconverting nanophosphors as biological labels[J].J Am Chem Soc,2008,130(10):3023-3029.
[9]CHIBA T,KITA K,ZHENG Y W,et al.Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J].Hepatology,2006,44(1):240-251.
[10]PHESSE T J,CLARKE A R.Normal stem cells in cancer prone epithelial tissues[J].Br J Cancer,2009,100(2):221-227.
[11]TODARO M,GAGGIANESI M,CATALANO V,et al.CD44v6is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis[J].Cell Stem Cell,2014,14(3):342-356.
[12]SHEN J,CHEN G,OHULCHANSKYY T Y,et al.Tunable near infrared to ultraviolet upconversion luminescence enhancement in(α-NaYF4:Yb,Tm)/CaF2core/shell nanoparticles for in situ real-time recorded biocompatible photoactivation[J].Small,2013,9(19):3213-3217.
[13]BARNI S,BERTONE V,SILOTTI M G,et al.Lysosomal exocytosis induced by hyperthermia:a new model of cancer death.III.Effect on liver metastasis[J].Biomed Pharmacother,1996,50(2):79-84.
[14]李韪韬,钱志余,李婷.组织热凝固程度无损监控的光学断层成像研究[J].光学学报,2010,20(1):169-174.
[15]张先增,王晓燕,詹振林,等.脉冲CO2激光与Er:YAG激光颅骨组织消融的比较[J].中国激光,2009,36(10):2577-2581.
[16]ZHOU A,WEI Y,WU B,et al.Pyropheophorbide a and c(RGDyK)comodified Chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy[J].Mol Pharm,2012,9(6):1580-1589.