Application of nanoparticles in cancer detection by Raman scattering based techniques

Figures & data

Figure 1. A typical Raman spectrum of a chemical compound and related peaks [10].

Figure 2. Schematic of the Raman spectra-imaging system. A 785 nm laser is used to illuminate the NP-stained tissue, creating a submillimeter-diameter laser spot. Raman-scattered photons from illuminated NPs are collected by multimode fibers and transmitted to a customized spectrometer (Andore Holospec®), where they are dispersed onto a cooled deep-depletion spectroscopic CCD. For raster scanning imaging, two axes are controlled through a custom LabVIEW program to translate the tissue sample. (b) A photograph of the raster-scanned tissue-imaging device. (c) A depiction of targeted SERS NPs and Biomarker-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have been explored as a viable option for targeting and imaging multiple cell-surface  biomarkers of cancer. (d) The Raman spectra of the various SERS NPs used in a related study [31].

Table 1. Some common nanoparticle structures, targeted cancer markers, and Raman reporters, in cancer detection using SERS.

Cancer marker	Detected cancer	SERS nanoparticle	Structure in brief	Detection specificity agent	RAMAN marker
PSMA [38]	Prostate	AuNPs	28nm popcorn-shaped (GNPOP)	PSMA antibody and A9 RNA anti-PSMA aptamer	Rh6G
HER2 [39]	Breast	AuNPs	GNPOP-attached SWCNT	S6 aptamer	Free dye labeling
CEA [40]	Lung	AuNPs	Hollow gold nano-spheres	CEA antibody	4,4′-DP
CEA [41]	Lung, prostate and others	Fe3O4-AuNPs	Fe3O4 NPs is coated with AuNPs	CEA antibody	4-ATP
CEA, AFP, CA12 [42]	Lung, prostate and others	Si@(AgNPs/PEI)	Cross-linking of small AgNPs at the surface of silica particle	Anti-CEA, anti-AFP and anti-CA125	4-ABT
FRs [43]	Various cancer types	g-C3N4/Au@ AgNPs	PEI functionalized g-C3N4 nanosheets and anchor the Au@AgNPs	Folic Acid	Rh6G
CD19 antigen [44]	Leukemia	AuNPs	Pegylated gold NPs	CD19 antibody	MGITC
EGFR [45]	Various cancer types	AuNPs	Immobilized SERS nanotag (MGITC bioconjugated AuNPs) in the core of hollow photonic crystal fiber	EGFR antibody	MGITC
CD34, SCA-1 [32]	Lung cancer	M-SERS DOTs	18nm magnetite in the core and AgNPs and silica as coating material	CD34-antibody, SCA1-antibody	4-MT and BT
CEA Tf [46]	CEA over expressed cancer cells (most of cancer cells)	PAH-PSS-Dye-GNRs	PAH layer on PSS layer create a two layer polyelectrolyte coated Gold Nan-Rods and Raman reporter directly connecting onto the surface of GNRs	CEA-8 and TfR	FITC, DTDC, DTTC, O170

Abbreviations: PSMA, prostate-specific membrane antigen; SWCNT, single wall carbon nanotube; Rh6G, rhodamine 6G; AuNP, gold nanoparticle; GNPOP, gold nano-popcorn; CEA, carcinoemberyonic antigen; 4,4′-DP, 4,4′-dipyridyl; FRs, folate receptors; g-C₃N₄, graphite- phase carbon nitride; AFP, alfa fetoprotein; CA125, carbohydrate antigen; DNBA, 5,5-dithiobis(2-nitrobenzoic acid); 4ATP, 4-aminothiophenol; MGITC, malachite green; CD34, cell differentiate antigen; SCA-1, stem cell antigen; 4-MT, 4-methyl benzenthiol; BT, benzenthiol; PSS, poly(styrene sulfonate); PAH, poly(allylamin hydrochloride); FITC, fluorescent isothiocyanate; DTTC, 3,3ˊ-diethylthiatricarbocyanine; DTDC, 3,3′-diethylthiadicarbocyanine; O170, oxazine170 perchlorate; GNRs, gold nanorod; Tf, transferrin; TfR, transferring; TF, transfer factor.

Figure 3. Schematic illustration of formation of sandwich structure and SERS HOT spot with both SERS tags (anti-CEA/4-ATP/Fe₃O₄-Au NPs) and SERS – active substrate [41].

Figure 4. Graph of estimated number of different cancer cases. Breast cancer is by far the highest incident type among females [3].

Figure 5. (a) Plot showing SERS. (b) Schematic representation shows the synthesis protocol for the formation of GNPOP attached SWCNTs [39].

Figure 6. Cancer cell targeting and spectroscopic detection by using antibody-conjugated SERS nanoparticles. (a) Preparation of targeted SERS nanoparticles by using a mixture of SH-PEG and a hetero-functional PEG (SH-PEG-COOH). Covalent conjugation of an EGFR-antibody fragment occurs at the exposed terminal of the hetero-functional PEG. (b) SERS spectra obtained from EGFR-positive cancer cells (Tu686) and from EGFR negative cancer cells (human non-small cell lung carcinoma NCI-H520) together with control data and the standard tag spectrum. All spectra were taken in cell suspension with 785-nm laser excitation and were corrected by subtracting the spectra of nanotag-stained cells by the spectra of unprocessed cells. The Raman reporter molecule is diethylthiatri-carbocyanine (DTTC), and its distinct spectral signatures are indicated by wave numbers (cm^–1) [71].

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