title: Engineering a cell-surface aptamer circuit for targeted and amplified photodynamic cancer therapy.
abstract: Photodynamic therapy is one of the most promising and noninvasive methods for clinical treatment of different malignant diseases. Here, we present a novel strategy of designing an aptamer-based DNA nanocircuit capable of selective recognition of cancer cells, controllable activation of photosensitizers, and amplification of photodynamic therapeutic effect. The aptamers can selectively recognize target cancer cells and bind to the specific proteins on cell membranes. Then the overhanging catalyst sequence on the aptamer can trigger a toehold-mediated catalytic strand displacement to activate the photosensitizer and achieve amplified therapeutic effect. The specific binding-induced activation allows the DNA circuit to distinguish diseased cells from healthy cells, reducing damage to nearby healthy cells. Moreover, the catalytic amplification reaction will only take place close to the target cancer cells, resulting in a high local concentration of singlet oxygen to selectively kill the target cells. The principle employed in this study demonstrated the feasibility of assembling a DNA circuit on cell membranes and could further broaden the utility of DNA circuits for applications in biology, biotechnology, and biomedicine.
authors: Center for Research at Bio/Nano Interface, Department of Chemistry, University of Florida, Gainesville, Florida 32611, United States.
authors: Da
authors: D
authors: Han
authors: Guizhi
authors: G
authors: Zhu
authors: Cuichen
authors: C
authors: Wu
authors: Zhi
authors: Z
authors: Zhu
authors: Tao
authors: T
authors: Chen
authors: Xiaobing
authors: X
authors: Zhang
authors: Weihong
authors: W
authors: Tan
mesh_terms: D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D057005:Bioengineering; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D026082:Singlet Oxygen
references: Cell. 2009 Feb 20;136(4):642-55
references: 19239886
references: ChemMedChem. 2008 Mar;3(3):425-8
references: 18058891
references: Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15275-8
references: 15492210
references: J Am Chem Soc. 2008 Aug 20;130(33):10856-7
references: 18661988
references: Nature. 1992 Feb 6;355(6360):564-6
references: 1741036
references: Nucleic Acids Res. 2011 Sep 1;39(16):e110
references: 21693555
references: Science. 1990 Aug 3;249(4968):505-10
references: 2200121
references: Leukemia. 2009 Feb;23(2):235-44
references: 19151784
references: Angew Chem Int Ed Engl. 2011 Jan 10;50(2):401-4
references: 21154791
references: J Am Chem Soc. 2005 Nov 30;127(47):16360-1
references: 16305199
references: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8989-94
references: 17502620
references: J Am Chem Soc. 2006 Apr 5;128(13):4200-1
references: 16568974
references: Mol Cells. 2005 Feb 28;19(1):1-15
references: 15750334
references: J Natl Cancer Inst. 1998 Jun 17;90(12):889-905
references: 9637138
references: Anal Chem. 2007 Jul 1;79(13):4900-7
references: 17530817
references: Chem Asian J. 2010 Apr 1;5(4):783-6
references: 20340154
references: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11838-43
references: 16873550
references: Nature. 1990 Mar 29;344(6265):467-8
references: 1690861
references: Science. 2007 Nov 16;318(5853):1121-5
references: 18006742
references: Science. 2011 Sep 2;333(6047):1307-11
references: 21885784
references: Biochemistry. 1995 Jan 17;34(2):656-65
references: 7819261
references: Nature. 1990 Aug 30;346(6287):818-22
references: 1697402
references: J Am Chem Soc. 2008 Aug 27;130(34):11268-9
references: 18680291
references: Nature. 2008 Jan 17;451(7176):318-22
references: 18202654
references: Photochem Photobiol Sci. 2011 Jul;10(7):1097-109
references: 21547329
references: J Am Chem Soc. 2004 Sep 22;126(37):11450-1
references: 15366886
references: ACS Nano. 2012 Jun 26;6(6):5070-7
references: 22631052
references: ChemMedChem. 2011 Oct 4;6(10):1778-80
references: 21774079
references: Anal Chem. 2008 Feb 1;80(3):721-8
references: 18177018
references: J Am Chem Soc. 2005 Nov 16;127(45):15664-5
references: 16277483