Protein-Templated Core/Shell Au Nanostructures for Intracellular Reactive Oxygen Species Detection by SERS

Abstract

Core/shell gold "raspberry" nanostructures capable of multiple therapeutic functionalities were synthesized using a template composed of monodispersed anionic protein (bovine serum albumin) nanoparticles coated with a cationic biopolymer (poly-L-lysine). The nanostructures exhibited high photothermal conversion efficiency when exposed to a near-infrared (NIR) laser, which led to significant cellular inhibition of A549 human lung cancer cells due to intracellular hyperthermia. The raspberry structures also provided hot spots for surface-enhanced Raman scattering (SERS) ratiometric sensing of intracellular reactive oxygen species (ROS) when modified with the Raman reporter molecule 4-aminothiophenol (4-ATP). ROS was detected in A549 lung cancer cells upon photothermal heating of internalized nanostructures, enabling a possible mechanism for feedback on therapeutic efficacy. This was confirmed by adding the antioxidant N-acetylcysteine (NAC) and using a complementary fluorescence technique, which showed that the amount of detectable intracellular ROS decreased. These safe-by-design gold raspberry nanostructures could be promising for simultaneous therapeutic applications and monitoring therapeutic efficacy.

SERS in 3D cell models: a powerful tool in cancer research

“…Based on the research progress so far, we can identify various areas that require further exploration, namely: (i) fully leveraging the capabilities of SERS for chemical and biomolecule identification in 3D, (ii) improving multiplexing possibilities, (iii) refining signal processing tools, (iv) addressing limitations towards clinical and practical implementation of SERS, and (v) expanding 3D SERS bioimaging and biosensing beyond 3D cancer models. While SERS has been successfully implemented for the quantitative detection in 2D of a multitude of analytes, including therapeutics, 245 neurotransmitters, 246 metabolites/proteins, [247][248][249] reactive oxygen species, 250,251 DNA, 252 pathogens, 253 and more, 200 still very few works take full advantage of the rich chemical information that SERS can provide in 3D systems. The implementation of label-free SERS in 3D models that recapitulate real biological environments or with ex/in vivo models, could provide key insights at the molecular level for early diagnosis and disease monitoring and/or for the development of novel therapies.…”

Coupling Au-loaded magnetic frameworks to photonic crystal for the improvement of photothermal heating effect in SERS

“…[6][7][8][9][10][11][12][13][14] Recently, numerous researchers have reported the potential role of the photothermal heating effect in SERS studies, however, the results are mixed. [15][16][17][18][19][20][21][22][23][24] For example, mild photothermal heating plays a positive role in SERS and has been widely employed in the eld of optical sensing and biological imaging. 25 On the other hand, the heat-induced degradation of analytes can produce carbonaceous species, cause desorption of the adsorbates in the excitation area, and lead to the catalytic transformation of analytes to produce other species.…”