Rational Design of Ultrabright SERS Probes with Embedded Reporters for Bioimaging and Photothermal Therapy

Abstract

Plasmonic nanoparticles can be utilized as surface-enhanced Raman scattering (SERS) probes for bioimaging and as photothermal (PT) agents for cancer therapy. Typically, their SERS and PT efficiencies reach maximal values under the on-resonant condition, when the excitation wavelength overlaps the localized surface plasmon resonance (LSPR) wavelength preferably in the near-infrared (NIR) biological window. However, the photogenerated heat may inevitably disturb or even destroy biological samples during the imaging process. Herein, we develop ultrabright SERS probes composed of metallic Au@Ag core-shell rodlike nanomatryoshkas (RNMs) with embedded Raman reporters. By rationally controlling the Ag shell thickness, the LSPR of RNMs can be tuned from UV to NIR range, resulting in highly tunable SERS and PT properties. As bright NIR SERS imaging nanoprobes, RNMs with a thick Ag shell are designed for minimal PT damage to the biological targets under the off-resonance condition, as illustrated through monitoring the changes in mitochondrial membrane potential of cancer cells during SERS imaging procedure. By contrast, RNMs with a thin Ag shell are designed as multifunctional NIR theranostic probes that combine enhanced photothermal therapy capability, as exemplified by efficient PT killing of cancer cells, with reduced yet still efficient imaging properties at the on-resonance excitation.

Surface‐Enhanced Raman Nanoprobes with Embedded Standards for Quantitative Cholesterol Detection

“…Transmission electron microscopy (TEM) imaging clearly demonstrates the spherical shape and the core–shell structure of the obtained Au@BDT@Ag NPs, with Ag shell of 11 ± 3 nm in thickness (Figure b,i). From the high resolution TEM image, it is confirmed that there is no distinct gap between the Au core and the Ag shell layer (Figure b,ii), which is consistent with our previous observation on Au@BDT@Ag core–shell rod‐like nanoprobes . The Au@BDT@Ag suspension shows a yellow color and the corresponding LSPR peak blueshifts to 426 nm (Figure c,iii), which further indicates the successful coating of the Ag shell .…”

“…We have additionally observed that a quite uniform nanogap can form inside Au@BDT@ Au NPs if a 1,4-BDT multilayer is embedded into the gap. [67] After careful examination of the literature [27,30,34,71] and our previous results, [38][39][40]63,67] we notice that the absence of clear gaps is a common feature in Au@molecule@Ag NPs with various particle shapes (e.g., nanosphere or nanorod) and embedded reporter molecules (e.g., 1,4-aminothiophenol, 4-mercaptobenzoic acid, cysteamine, and 1,4-BDT). The existence of the nanogap seems greatly connected to the metal of the external shell, for example, Au or Ag.…”

“…From the high resolution TEM image, it is confirmed that there is no distinct gap between the Au core and the Ag shell layer ( Figure 2b,ii), which is consistent with our previous observation on Au@BDT@Ag core-shell rod-like nanoprobes. [63] The Au@BDT@Ag suspension shows a yellow color and the corresponding LSPR peak blueshifts to 426 nm (Figure 2c,iii), which further indicates the successful coating of the Ag shell. [27,64,65] The calculated extinction spectrum of a Au@Ag core-shell NP (24 nm for the diameter of the Au core and 20 nm for the Ag shell thickness, without internal gaps in the simulation model) by the finite difference time domain (FDTD) method well fits the experimental extinction spectrum (dashed line in Figure 2c), which also suggests that no internal gaps exist in the Au@BDT@Ag NPs.…”

Raman photostability of off-resonant gap-enhanced Raman tags

“…28 This important feature has been conrmed before by the high-resolution TEM but without a clear explanation yet. 28,34 The corresponding high-resolution inverted TEM images of GERTs are shown in the insets of Fig. 1a, which further conrm the observation of the gap morphology above.…”

“…We have synthesized ve different types of GERTs, either with different embedded Raman reporter molecules, shell thicknesses, or nanoparticle (NP) shapes using the slightly modied procedures we described before. 22,28 Fig. 1a shows the schematic illustration of GERTs and the corresponding molecular structures of embedded Raman reporters:…”