title: Stimulated Raman scattering microscopy: an emerging tool for drug discovery.
abstract: Optical microscopy techniques have emerged as a cornerstone of biomedical research, capable of probing the cellular functions of a vast range of substrates, whilst being minimally invasive to the cells or tissues of interest. Incorporating biological imaging into the early stages of the drug discovery process can provide invaluable information about drug activity within complex disease models. Spontaneous Raman spectroscopy has been widely used as a platform for the study of cells and their components based on chemical composition; but slow acquisition rates, poor resolution and a lack of sensitivity have hampered further development. A new generation of stimulated Raman techniques is emerging which allows the imaging of cells, tissues and organisms at faster acquisition speeds, and with greater resolution and sensitivity than previously possible. This review focuses on the development of stimulated Raman scattering (SRS), and covers the use of bioorthogonal tags to enhance sample detection, and recent applications of both spontaneous Raman and SRS as novel imaging platforms to facilitate the drug discovery process.
authors.affiliation: EaStCHEM School of Chemistry, The University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, UK. Alison.Hulme@ed.ac.uk.
authors.forename: W J
authors.initials: WJ
authors.lastname: Tipping
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Serrels
authors.forename: V G
authors.initials: VG
authors.lastname: Brunton
authors.forename: A N
authors.initials: AN
authors.lastname: Hulme
mesh_terms: D055808:Drug Discovery; D008853:Microscopy / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods*
references.citation: J Am Chem Soc. 2012 Dec 26;134(51):20681-9
references.pmid: 23198907
references.citation: Nat Rev Drug Discov. 2011 Jun 24;10(7):507-19
references.pmid: 21701501
references.citation: Science. 2013 Aug 16;341(6147):752-8
references.pmid: 23950532
references.citation: J Biophotonics. 2013 Oct;6(10):803-14
references.pmid: 23303610
references.citation: Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7725-30
references.pmid: 26056283
references.citation: ACS Nano. 2014 Apr 22;8(4):3421-6
references.pmid: 24601546
references.citation: Angew Chem Int Ed Engl. 2009;48(38):6974-98
references.pmid: 19714693
references.citation: Science. 2010 Dec 3;330(6009):1368-70
references.pmid: 21127249
references.citation: Drug Discov Today. 2014 Mar;19(3):341-7
references.pmid: 24269835
references.citation: Nat Rev Clin Oncol. 2010 Dec 07;8(4):200-9
references.pmid: 21135887
references.citation: Bioorg Med Chem Lett. 2014 Nov 1;24(21):5098-101
references.pmid: 25266783
references.citation: Angew Chem Int Ed Engl. 2015 Aug 17;54(34):9821-5
references.pmid: 26207979
references.citation: Angew Chem Int Ed Engl. 2014 May 26;53(22):5596-9
references.pmid: 24737659
references.citation: Nat Rev Drug Discov. 2005 Feb;4(2):161-5
references.pmid: 15688078
references.citation: Org Lett. 2006 Aug 17;8(17):3639-42
references.pmid: 16898780
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11226-31
references.pmid: 23798434
references.citation: J Am Chem Soc. 2014 Jun 18;136(24):8820-8
references.pmid: 24869754
references.citation: Intravital. 2015 Jun 8;4(1):e1055430
references.pmid: 28243514
references.citation: Mol Pharm. 2011 Jun 6;8(3):969-75
references.pmid: 21548600
references.citation: Mol Pharm. 2011 Feb 7;8(1):176-84
references.pmid: 21053973
references.citation: Analyst. 2014 Mar 7;139(5):1155-61
references.pmid: 24427772
references.citation: Nat Rev Drug Discov. 2014 Jun;13(6):433-44
references.pmid: 24833295
references.citation: Nat Rev Drug Discov. 2009 Dec;8(12):959-68
references.pmid: 19949401
references.citation: Nat Rev Drug Discov. 2004 Aug;3(8):711-5
references.pmid: 15286737
references.citation: J Am Chem Soc. 2014 Jun 4;136(22):8027-33
references.pmid: 24849912
references.citation: Angew Chem Int Ed Engl. 2006 Nov 13;45(44):7364-7
references.pmid: 17036290
references.citation: Angew Chem Int Ed Engl. 2010 Apr 26;49(19):3310-2
references.pmid: 20349485
references.citation: Nat Protoc. 2012 Sep;7(9):1694-708
references.pmid: 22918387
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Apr 1;848(2):379-83
references.pmid: 17101305
references.citation: Opt Express. 2013 Jun 3;21(11):13864-74
references.pmid: 23736639
references.citation: Bioorg Med Chem Lett. 2015 Feb 1;25(3):664-7
references.pmid: 25522818
references.citation: ACS Nano. 2009 Nov 24;3(11):3552-9
references.pmid: 19863088
references.citation: Nat Rev Cancer. 2014 May;14(5):314-28
references.pmid: 24739578
references.citation: Nat Methods. 2014 Apr;11(4):410-2
references.pmid: 24584195
references.citation: Pharm Res. 2008 Jan;25(1):87-103
references.pmid: 17985216
references.citation: Anal Chem. 2013 May 21;85(10):5055-63
references.pmid: 23581493
references.citation: Front Plant Sci. 2014 Apr 23;5:140
references.pmid: 24795734
references.citation: Nat Rev Drug Discov. 2011 Jun;10(6):428-38
references.pmid: 21629293
references.citation: Rapid Commun Mass Spectrom. 2005;19(18):2507-16
references.pmid: 16106343
references.citation: Nat Rev Drug Discov. 2010 Mar;9(3):203-14
references.pmid: 20168317
references.citation: Mol Pharm. 2012 Apr 2;9(4):930-6
references.pmid: 22376068
references.citation: ACS Chem Biol. 2015 Mar 20;10(3):901-8
references.pmid: 25560305
references.citation: J Cell Sci. 2011 Sep 1;124(Pt 17):2877-90
references.pmid: 21878495
references.citation: Expert Opin Drug Discov. 2013 Apr;8(4):363-8
references.pmid: 23373702
references.citation: Nat Photonics. 2011;5(2):103-109
references.pmid: 23015809
references.citation: Analyst. 2014 May 21;139(10):2312-7
references.pmid: 24555181
references.citation: J Am Chem Soc. 2010 Jan 27;132(3):980-8
references.pmid: 20041639
references.citation: Science. 2008 Dec 19;322(5909):1857-61
references.pmid: 19095943
references.citation: Nature. 2008 Apr 3;452(7187):580-9
references.pmid: 18385732
references.citation: Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50
references.pmid: 22508028
references.citation: Pharmaceutics. 2011 Apr 04;3(2):141-70
references.pmid: 24310493
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):10821-6
references.pmid: 22711807
references.citation: J Clin Oncol. 2001 Jul 1;19(13):3267-79
references.pmid: 11432895
references.citation: Nat Rev Drug Discov. 2005 May;4(5):410-20
references.pmid: 15864270
references.citation: Chem Soc Rev. 2016 Apr 7;45(7):1819-49
references.pmid: 26497570
references.citation: Expert Opin Drug Discov. 2012 Oct;7(10):863-75
references.pmid: 22992175
references.citation: Mol Pharm. 2011 Oct 3;8(5):1742-9
references.pmid: 21800872
references.citation: J Biophotonics. 2015 Jul;8(7):527-45
references.pmid: 25220508
references.citation: Rapid Commun Mass Spectrom. 2010 Nov 30;24(22):3309-19
references.pmid: 20973006
references.citation: Bioorg Med Chem. 2015 Jul 1;23(13):2989-94
references.pmid: 26026768
references.citation: Drug Discov Today. 2014 Feb;19(2):164-70
references.pmid: 24055840
references.citation: J Am Chem Soc. 2008 Oct 15;130(41):13540-1
references.pmid: 18803379
references.citation: J Phys Chem B. 2013 Apr 25;117(16):4634-40
references.pmid: 23256635
references.citation: J Biomed Opt. 2014;19(11):111604
references.pmid: 24858033
references.citation: Mol Pharm. 2008 Mar-Apr;5(2):287-93
references.pmid: 18197626
references.citation: Sci Rep. 2015 Jan 22;5:7930
references.pmid: 25608867
references.citation: Analyst. 2010 Oct;135(10):2613-9
references.pmid: 20625604
references.citation: J Mater Chem B. 2013 Dec 7;1(45):6302-6311
references.pmid: 32261703
references.citation: Bioorg Chem. 2007 Jun;35(3):284-93
references.pmid: 17316745
references.citation: Methods. 2014 Jul 1;68(2):283-5
references.pmid: 24881809
references.citation: Anal Chem. 2013 Jan 2;85(1):98-106
references.pmid: 23198914
references.citation: Nat Med. 2013 Jun;19(6):656
references.pmid: 23744136
references.citation: J Control Release. 2014 Jan 28;174:37-42
references.pmid: 24231405
references.citation: Anal Bioanal Chem. 2009 Jun;394(3):707-29
references.pmid: 19184676
references.citation: Chem Commun (Camb). 2014 Feb 9;50(11):1341-3
references.pmid: 24346645
references.citation: Angew Chem Int Ed Engl. 2014 Oct 27;53(44):11787-92
references.pmid: 25195517
references.citation: Science. 2013 Aug 16;341(6147):742-6
references.pmid: 23950530
references.citation: Biochemistry. 2014 Jul 1;53(25):4113-21
references.pmid: 24901294
references.citation: J Control Release. 2012 Jul 20;161(2):656-67
references.pmid: 22465394
references.citation: Small. 2011 Mar 21;7(6):812-9
references.pmid: 21302355
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20404-9
references.pmid: 22143759
references.citation: Analyst. 2013 Oct 7;138(19):5627-38
references.pmid: 23897394
references.citation: Annu Rev Phys Chem. 2011;62:507-30
references.pmid: 21453061
references.citation: Eur J Pharmacol. 2008 May 13;585(2-3):292-302
references.pmid: 18420192
references.citation: Bioorg Med Chem Lett. 2013 Nov 1;23(21):5980-91
references.pmid: 24018190
references.citation: J Med Chem. 2010 Nov 25;53(22):7902-17
references.pmid: 20804202
references.citation: Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11624-9
references.pmid: 26324899
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2415-20
references.pmid: 18272492
references.citation: Drug Discov Today. 2014 May;19(5):688-93
references.pmid: 24451294
references.citation: Angew Chem Int Ed Engl. 2013 Dec 2;52(49):13042-6
references.pmid: 24127161
references.citation: Nat Chem. 2014 Jul;6(7):614-22
references.pmid: 24950332
references.citation: Anal Chem. 2008 Dec 15;80(24):9576-82
references.pmid: 19006335
references.citation: Chem Biol. 2012 Nov 21;19(11):1373-80
references.pmid: 23177192
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16807-12
references.pmid: 16263923
references.citation: Angew Chem Int Ed Engl. 2014 Jun 2;53(23):5827-31
references.pmid: 24753329
references.citation: Anal Chem. 2013 Nov 19;85(22):10697-701
references.pmid: 24083399
references.citation: J Am Chem Soc. 2011 Apr 27;133(16):6102-5
references.pmid: 21443184
references.citation: Nature. 1990 Sep 20;347(6290):301-3
references.pmid: 2205805
references.citation: Appl Spectrosc. 2012 Jun;66(6):644-9
references.pmid: 22732534
references.citation: Nat Rev Drug Discov. 2006 May;5(5):387-98
references.pmid: 16672925