New Insight of Tetraphenylethylene-based Raman Signatures for Targeted SERS Nanoprobe Construction Toward Prostate Cancer Cell Detection

Abstract

We have designed and synthesized novel tetraphenylethylene (TPE) appended organic fluorogens and unfold their unique Raman fingerprinting reflected by surface-enhanced Raman scattering (SERS) upon adsorption on nanoroughened gold surface as a new insight in addition to their prevalent aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) phenomena. A series of five TPE analogues has been synthesized consisting of different electron donors such as (1) indoline with propyl (TPE-In), (2) indoline with lipoic acid (TPE-In-L), (3) indoline with Boc-protected propyl amine (TPE-In-Boc), (4) benzothaizole (TPE-B), and (5) quinaldine (TPE-Q). Interestingly, all five TPE analogues produced multiplexing Raman signal pattern, out of which TPE-In-Boc showed a significant increase in signal intensity in the fingerprint region. An efficient SERS nanoprobe has been constructed using gold nanoparticles as SERS substrate, and the TPE-In as the Raman reporter, which conjugated with a specific peptide substrate, Cys-Ser-Lys-Leu-Gln-OH, well-known for the recognition of prostate-specific antigen (PSA). The designated nanoprobe TPE-In-PSA@Au acted as SERS "ON/OFF" probe in peace with the vicinity of PSA protease, which distinctly recognizes PSA expression with a limit of detection of 0.5 ng in SERS platform. Furthermore, TPE-In-PSA@Au nanoprobe was efficiently recognized the overexpressed PSA in human LNCaP cells, which can be visualized through SERS spectral analysis and SERS mapping.

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

“…Gold NPs (AuNPs) in the form of nano-cages, -spheres, -beacons, -stars, -shells, -seeds, -sheets, or nanorods is being evaluated in many different settings, for example, for both PCa and BC (Figure 2) [8,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141]. By changing the AuNPs’ shape, size, or surface characteristics it is possible to fine-tune their properties in order to maximize their applicability as a tool for cancer diagnosis, photo-dynamic/thermal therapy, therapy-drug carrier, radiotherapy drug enhancer, targeted gene therapy, or as a combined theranostic nanovehicle [142,143,144,145,146,147,148,149,150,151,152,153,154,155].…”

“…Mkandawire et al have recently investigated an alternative way to treat BC cells inducing apoptosis by targeting their mitochondria using AuNPs during photothermal treatment [164]. Regarding tumor detection, surface enhanced Raman spectroscopy (SERS) can be used for in vivo applications, and some studies have been performed recent years investigating its applicability for PCa and BC [129,161,166,167,168,169,170]. Ramaya et al investigated the overexpression of prostate specific antigen (PSA) in LNCaP cells by using tetraphenylethylene (TPE) appended organic fluorogens adsorbed on AuNPs.…”

Development of a SERS Probe for Selective Detection of Healthy Prostate and Malignant Prostate Cancer Cells Using ZnII

“…In addition, SERS provides several advantages over fluorescence-based assays 21–30 and these are as follows: 1) near IR light can be easily used to avoid tissue autofluorescence and to enhance significantly the tissue penetration depth; (2) very narrow spectral widths in Raman bands allow multiple labels detection under single NIR light source and (3) due to the non-resonance condition, photo-bleaching issues are minimum for SERS. Since SERS has capability for non-destructive in vivo measurements with relatively large penetration depth, scientists are developing Raman probes which can be used for diagnostic accuracy, speed and cost-effective in-vivo sensing of cancer 20–23, 26, 29–31 .…”

“…As shown in Figure 1A and Figure 2A, in the presence of Zn(II), gold nanoparticle forms assembly structure via the formation of co-ordination bond between Zn(II) and p-(imidazole)azo) benzenethiol Raman reporter. In the assembly structure, Raman reporter attached gold nanoparticle forms “hot spots”, which enhances the electromagnetic field coupling of plasmonic particles via light-matter interaction 23–32 . Since the presence of Zn(II) enhances the SERS signal intensity tremendously, our reported experimental data show that the detection limit for Zn(II) can be as low as 10 parts per trillion (ppt).…”

Unveiling NIR Aza‐Boron‐Dipyrromethene (BODIPY) Dyes as Raman Probes: Surface‐Enhanced Raman Scattering (SERS)‐Guided Selective Detection and Imaging of Human Cancer Cells

“…[17,18] For instance, al abel-freeb lood test method basedo nS ERS was reportedf or nasopharyngeal,gastric and colorectal cancer detection. [26][27][28] Despite the diverse attempts to discover new Raman reporter molecules, mosto ft he reported approaches suffer from several disadvantages such as low resolution, short wavelength absorption and high fluorescenceb ackground, which may mask the Raman signals. In addition to the frequentlyu sed commerciallya vailable Ramanr eporters such as crystal violet (CV), malachite green isothiocyanate (MGITC), 4-mercaptobenzoic acid (4-MBA), Rhodamine 6G, and diethylthiatricarbocyanine (DTTC), there has been increased interest in the development of new Ramans ignature molecules for diversed iagnostic and imaging applications.…”