Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions

Abstract

The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepared and stored in aqueous solution, have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze−thawing, lyophilization, heating, and physiological conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiological buffer solutions. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar experimental conditions. This additional enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of molecular ligands for tumor targeting.In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανβ3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for preparing SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.

Behavior of Citrate-Capped Ultrasmall Gold Nanoparticles on a Supported Lipid Bilayer Interface at Atomic Resolution

“…The inability of the AuNP to successfully embed completely within the gel-phase bilayer (i.e., interfacial interaction) has potential implications for other hard–soft matter or lipid–NP interactions and other biological–bilayer interactions, as other materials with similar properties may exhibit similar behavior. The ability of the AuNP to localize within the central core of the fluid-phase bilayer has potential applications in targeting specific membrane embedded protein anchorage motifs (i.e., nonpolar/hydrophobic regions of proteins). , Specificity of these domains and functionality can be further enhanced via AuNP–protein/peptide conjugation, − while cell penetration can be enhanced via alteration of ligand coating and conjugation to cell-penetrating peptides . The ability of the AuNP to potentially translocate across the gel-phase bilayer upper leaflet surface allows it to potentially illicit effects and/or delivery compounds to the cell without direct interference with intracellular organelles or other cellular constituents.…”

Au Atoms Anchored on Amorphous C3N4 for Single-Site Raman Enhancement

“…Surface-enhanced Raman scattering (SERS) as high-sensitive molecular fingerprint spectroscopy has been widely used in surface/interface analysis, molecular detection, and chemical sensing. − Traditional SERS substrates are based on noble metals, which can yield large electromagnetic enhancement (EE) and achieve high enhancement factors based on the surface plasmon resonance (SPR) effect (mainly lies in the “hotspots” at the gaps between noble-metal particles). − However, the EE-based noble-metal SERS substrates suffer from poor biocompatibility, excessive cost, and inferior spectral stability and reproducibility stemming from the uneven distribution of hot spots, which seriously hinder their practical applications. Other plasmon-free SERS substrates are based on the chemical enhancement (CE) mechanism involving the efficient photoinduced charge transfer between substrates and probe molecules, which enlarge molecular polarizability tensor and magnify Raman scattering cross sections. − CE-based semiconductor SERS substrates have garnered tremendous attention owing to their high spectral stability and good biocompatibility, such as Cu 2 O, ZnO, TiO 2 , etc. − Nevertheless, how to effectively promote the interface charge transfer and further enhance the Raman signal is still a big challenge.…”

Simultaneous Visualization of Dual Intercellular Signal Transductions via SERS Imaging of Membrane Proteins Dimerization on Single Cells

“…To address these issues, surface-enhanced Raman scattering is expected to provide very exciting solutions, which offers a “signature” spectrum profile of the molecule with good photostability and is known as a powerful tool for reliable, easy-to-operate, ultrasensitive analysis of trace substances (even a single molecule) with excellent capability to simultaneously detect multiple analytes due to the very narrow characteristic Raman peak. , In recent years, some SERS detections of protein biomarkers on cell membranes were reported. − However, there is no report on SERS-based imaging of in situ protein dimerization on live cells, and the key is to develop highly sensitive and specific SERS detection strategies, especially for multianalysis. Herein, as proof-of-principle, the protein kinase receptors (i.e., mesenchymal-epithelial transition factor (Met) and transforming growth factor-β type II receptor (TβRII), known as the receptors for hepatocyte growth factor (HGF) and transforming growth factor Beta 1 (TGFβ1), respectively) , are selected for the multianalysis model of HGF- and TGFβ1-based intercellular signal transductions, and a highly sensitive SERS strategy for facile and simultaneously imaging two signal transductions via membrane proteins dimerizations was proposed for the PLA catalytic hairpin assembly (CHA)-based networking of AuNPs-based dual-recognition probes (dual-RPs) and SERS tags on live cells.…”