Tissue Engineering And Nanotheranostics

b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”

186 Tissue Engineering and Nanotheranostics

nanodumbbell. This interparticle nanogap structure offers high

enhancement factor (EF) values (>10^12 ) to achieve single­molecule sen­

sitivity. To overcome the limit of silver layer deposition, Nam’s et al.^192

propose creative DNA­based monomeric gold nanobridged nanogap

(Au–NNPs) structures (Fig. 8(b)) with approximately 1­nm interior

gap. SERs signals generated by Au–NNPs showed a linear depend­

ence on probe concentration (R 2 > 0.98) and were sensitive down to

10 fM concentrations. Yields of Au–NNPs is higher than 95%, and

>90% of Au–NNPs had EFs greater than 10^8 which is sufficient for

single­molecular detection.

SERs tag, referred to as SERS­encoded nanoparticles, is com­

posed of the SERs substrate, usually single plasmonic nanoparticles or

coupled plasmonic nanoparticles, and reporter, usually a molecular

label with high Raman cross­section, and an acceptor which is capable

of binding the analyst.193–195

SERs tag could be designed to serve as a pH marker of a cellular

microenvironment, especially for the tumor microenvironment since

acidity is the hallmark for solid tumors due to the high glucose

metabolism rate and poor vascular perfusion. Vo­Dinh’s et al.^196

developed a pH sensing SERS nanoprobe based on gold Nanostructures

and para­mercaptobenzoic acid (pMBA) as the reporter, the SERS

peak intensity at 1700 cm–1 decreases while SERS intensity of peaks at

1014 cm–1, 1136 cm–1, or 1390 cm–1 increases when pH changes from

5 to 9. Therefore, pH sensor is also used to probe an image of pH in

live cells with subcellular resolution.^197

A lot of biomolecules (e.g. peptides, proteins, antibodies,

antibody fragments, DNA) could be conjugated with SERs sub­

strate for molecular imaging application. For example, anti­EGFR

antibody/antibody single­chain variable fragment has been modi­

fied on AuNP to detect EGFR in human cancer cells and xenograft

tumor models.198–200 By using fluorescent SERS nanoparticles

(F–SERs dots), dynamic physiological process of cells, like apopto­

sis, could be monitored. F­SERs dots conjugate annexin V, anti­Bad

or anti­Bax antibodies were used for multiparametric analysis of

apoptosis. It has been proved that F–SERs dots have little toxicity

and could analysis apoptosis in both cells and tissues by both