title: Aggregation induced Raman scattering of squaraine dye: Implementation in diagnosis of cervical cancer dysplasia by SERS imaging.
abstract: The extent of squaraine dye aggregation that reflects on surface enhanced Raman signal scattering (SERS) intensity upon adsorption on nano-roughened gold surface has been investigated. Here we have synthesized a serious of six squaraine dyes consisting of two different electron donor moiety i.e. 1,1,2-trimethyl-1H-benzo[e]indole and 2-methylbenzo[d]thiazole which modulates the chemisorptions and hydrophobicity being designated as SQ1, SQ2, SQ3, SQ4, SQ5 and SQ6. Interestingly, SQ2 (mono lipoic acid appended), SQ5 and SQ6 (conjugated with hexyl and dodecyl side chain) squaraine derivatives having more tendency of aggregation in DMSO-water mixed solvent showed significant increase of Raman scattering in the fingerprint region when chemisorbed on spherical gold nanoparticles. Two sets of SERS nanotags were prepared with colloidal gold nanoparticle (Au-NPs size: 40 nm) by incorporating Raman reporters SQ2 and SQ5 followed by thiolated PEG encapsulation (SH-PEG, SH-PEG-COOH) denoted as AuNPs-SQ2-PEG and AuNPs-SQ5-PEG. Further conjugation of these nanotag with monoclonal antibodies specific to over expressed receptors, EGFR and p16/Ki-67 in cervical cancer cell, HeLa showed prominent SERS mapping intensity and selectivity towards cell surface and nucleus. The fast and accurate recognition obtained by antibody triggered SERS-nanotag has been compared with conventional time consuming immunocytochemistry technique which prompted us to extend further investigation using real patient cervical smear sample for a non-invasive, ultrafast and accurate diagnosis.
authors: CSIR-National Institute for Interdisciplinary Science & Technology (NIIST), Chemical Science & Technology Division (CSTD), Organic Chemistry Section, Industrial Estate, Thiruvananthapuram 695019, Kerala, India.
authors: Nisha
authors: N
authors: Narayanan
authors: CSIR-National Institute for Interdisciplinary Science & Technology (NIIST), Chemical Science & Technology Division (CSTD), Organic Chemistry Section, Industrial Estate, Thiruvananthapuram 695019, Kerala, India.
authors: Varsha
authors: V
authors: Karunakaran
authors: Sree Chitra Tirunal Institute for Medical Sciences & Technology, FADDS, Biomedical Technology Wing, Poojappura, Thiruvananthapuram 695012, Kerala, India.
authors: Willi
authors: W
authors: Paul
authors: CSIR-NIIST, CSTD, Photosciences and Photonics Section, India.
authors: Karunakaran
authors: K
authors: Venugopal
authors: Regional Cancer Centre (RCC), Division of Cancer Research, Thiruvananthapuram 695011, Kerala, India.
authors: K
authors: K
authors: Sujathan
authors: CSIR-National Institute for Interdisciplinary Science & Technology (NIIST), Chemical Science & Technology Division (CSTD), Organic Chemistry Section, Industrial Estate, Thiruvananthapuram 695019, Kerala, India. Electronic address: kkmaiti@niist.res.in.
authors: Kaustabh
authors: K
authors: Kumar Maiti
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004396:Coloring Agents; D003503:Cyclobutanes; D005260:Female; D006046:Gold / Q000737:chemistry; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008027:Light; D053768:Metal Nanoparticles / Q000737:chemistry*; D057054:Molecular Imaging / Q000379:methods; D010636:Phenols; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004396:Coloring Agents; D003503:Cyclobutanes; D010636:Phenols; C480596:squaraine; D006046:Gold
keywords: Aggregation; Immunocytochemistry; Raman mapping; Raman scattering; SERS nanotag; Squaraine dye