Tumor exosomes with molecular marker-proteins inherited from their parent cells have emerged as a promising liquid biopsy biomarker for cancer diagnosis. However, facile, robust, and sensitive detection of exosomal proteins remains challenging. Therefore, a nanozyme sensor array is constructed by using aptamer-modified C3N4 nanosheets (Apt/C3N4 NSs) together with a solvent-mediated signal amplification strategy for ratiometric fluorescence detection of exosomal proteins. Three aptamers specific to exosomal proteins are selected to construct Apt/C3N4 NSs for high specific recognition of exosomal proteins. The adsorption of aptamers enhances the catalytic activity of C3N4 NSs as a nanozyme for oxidation of o-phenylenediamine (oPD) to 2,3-diaminophenazine (DAP). In the presence of target exosomes, the strong affinity between aptamer and exosome leads to the disintegration of Apt/C3N4 NSs, resulting in a decrease of catalytic activity, thereby reducing the production of DAP. The ratiometric fluorescence signal based on a photoinduced electron transfer (PET) effect between DAP and C3N4 NSs is dependent on the concentration of DAP generated, thus achieving highly facile and robust detection of exosomal proteins. Remarkably, the addition of organic solvent-1,4-dioxane can sensitize the luminescence of DAP without affecting the intrinsic fluorescence of C3N4 NSs, achieving the amplification of the aptamer-exosome recognition events. The detection limit for exosome is 2.5 × 103 particles/mL. In addition, the accurate identification of cancer can be achieved by machine learning algorithms to analyze the difference of exosomal proteins from different patients’ blood. We hope that this facile, robust, sensitive, and versatile nanozyme sensor array would become a promising tool in the field of cancer diagnosis.

Exosomes are expected to be used as cancer biomarkers because they carry a variety of cancer-related proteins inherited from parental cells. However, it is still challenging to develop a sensitive, robust, and high-throughput technique for simultaneous detection of exosomal proteins. Herein, three aptamers specific to cancer-associated proteins (CD63, EpCAM, and HER2) are selected to connect gold nanoparticles (AuNPs) as core with three different elements (Y, Eu, and Tb) doped up-conversion nanoparticles (UCNPs) as satellites, thereby forming three nanosatellite assemblies. The presence of exosomes causes specific aptamers to recognize surface proteins and release the corresponding UCNPs, which can be simultaneously detected by inductively coupled plasma–mass spectrometry (ICP–MS). It is worth noting that rare earth elements are scarcely present in living systems, which minimize the background for ICP–MS detection and exclude potential interferences from the coexisting species. Using this method, we are able to simultaneously detect three exosomal proteins within 40 min, and the limit of detection for exosome is 4.7 × 103 particles/mL. The exosomes from seven different cell lines (L-02, HepG2, GES-1, MGC803, AGS, HeLa, and MCF-7) can be distinguished with 100% accuracy by linear discriminant analysis. In addition, this analytical strategy is successfully used to detect exosomes in clinical samples to distinguish stomach cancer patients from healthy individuals. These results suggest that this sensitive and high-throughput analytical strategy based on ICP–MS has the potential to play an important role in the detection of multiple exosomal proteins and the identification of early cancer.

Lipid droplets (LDs) are intracellular lipid-rich organelles, which not only serve as neutral lipid reservoirs but also involve in many physiological processes and are associated with a variety of metabolic diseases and cancers. Long-term tracking of the state and behavior of LDs is of great significance but challenging. The difficulty is largely due to the lack of low cytotoxicity, high photobleaching resistance, and long intracellular retention probes that are capable of long-term tracking LDs. Herein, we report the discovery of two amphiphilic LD-targeting carbon nanoparticles (CNPs, i.e., CPDs and CDs) prepared by one-step room-temperature and hydrothermal methods. Their high lipid–water partition coefficient (log P > 2.13) and strong positive solvatochromism property ensure the quality of LD imaging. Especially, CDs exhibit favorable biocompatibility (2 mg mL–1, cell viability >90%), excellent photostability (after continuous laser irradiation on a confocal microscope for 2 h, relative FL intensity >85%), and superior intracellular retention ability, thereby enabling long-term tracking of LDs in hepatocytes for up to six passages. Based on the excellent long-term tracking ability, CDs are successfully applied to observe autophagy in a typical catabolic process and to evaluate the effect of a commonly used lipid-lowering drug atorvastatin on hepatocyte lipid uptake.

Triple optical response of a nano-composite facilitates discrimination of antibiotic-resistant Gram-negative bacteria from normal ones based on a sensing array technique.