Detection of cancer-related exosomes in body fluids has become a revolutionary strategy for early cancer diagnosis and prognosis prediction. We have developed a two-step targeting detection method, termed PS-MIPs-NELISA SERS, for rapid and highly sensitive exosomes detection. In the first step, a phospholipid polar site imprinting strategy was employed using magnetic PS-MIPs (phospholipids-molecularly imprinted polymers) to selectively isolate and enrich all exosomes from urine samples. In the second step, a nanozyme-linked immunosorbent assay (NELISA) technique was utilized. We constructed Au/Na7PMo11O39 nanoparticles (NPs) with both surface-enhanced Raman scattering (SERS) property and peroxidase catalytic activity, followed by the immobilization of CD9 antibodies on the surface of Au/Na7PMo11O39 NPs. The Au/Na7PMo11O39-CD9 antibody complexes were then used to recognize CD9 proteins on the surface of exosomes enriched by magnetic PS-MIPs. Lastly, the high sensitivity detection of exosomes was achieved indirectly via the SERS activity and peroxidase-like activity of Au/Na7PMo11O39 NPs. The quantity of exosomes in urine samples from pancreatic cancer patients obtained by the PS-MIPs-NELISA SERS technique showed a linear relationship with the SERS intensity in the range of 6.21 × 107-2.81 × 108 particles/mL, with a limit of detection (LOD) of 5.82 × 107 particles/mL. The SERS signal intensity of exosomes in urine samples from pancreatic cancer patients was higher than that of healthy volunteers. This bidirectional MIPs-NELISA-SERS approach enables noninvasive, highly sensitive, and rapid detection of cancer, facilitating the monitoring of disease progression during treatment and opening up a new avenue for rapid early cancer screening.
Biosensing Techniques , Exosomes , Gold , Spectrum Analysis, Raman , Humans , Exosomes/chemistry , Gold/chemistry , Spectrum Analysis, Raman/methods , Phospholipids/chemistry , Phospholipids/urine , Limit of Detection , Molecular Imprinting , Molecularly Imprinted Polymers/chemistry , Epitopes/immunology , Epitopes/chemistry , Metal Nanoparticles/chemistry , Tetraspanin 29/urine , Tetraspanin 29/analysis , Antibodies, Immobilized/chemistry
Although there has been intense research on plasmon-induced charge transfer within metal/semiconductor heterostructures, previous studies have all focused on the surface plasmonic resonance (SPR) of only noble metals. Herein and for the first time, we observe and take into account the plasmonic coupling between SPR of both noble-metal and semiconductor nanostructures. A W18O49/Ag heterostructure composed of metallic Ag nanoparticles (Ag NPs) and semiconducting W18O49 nanowires (W18O49 NWs) is designed and fabricated, which exhibits a broad and strong SPR absorption in the visible wavelength range. This SPR band is attributed to the SPR coupling between the SPR of both Ag NPs and W18O49 NWs. Surface-enhanced Raman scattering (SERS) is then used to reveal the interactions between the metal SPR, semiconductor SPR, and the heterostructure's charge transfer (CT) process, demonstrating that such coupled SPR enhanced the heterostructure's internal CT and SERS signals. Finally, we proposed a new coupled-plasmon-induced charge transfer mechanism to interpret the improved CT efficiency between the SERS substrate and molecules. Our work provides insight for further studies on plasmonic effects and interfacial charge transfer in metal/semiconductor heterostructures.
