Nanoplasmonic Sandwich Immunoassay for Tumor-Derived Exosome Detection and Exosomal PD-L1 Profiling

Wang, Chuanyu; Huang, Chung-Hui; Gao, Zhuangqiang; Shen, Jialiang; He, Jiacheng; MacLachlan, Alana; Ma, Caihong; Chang, Yanan; Yang, Wen; Cai, Yuxin; Lou, Yang; Dai, Siyuan; Chen, Weiqiang; Li, Feng; Chen, Pengyu

doi:10.1021/acssensors.1c01101

Cited by 39 publications

(32 citation statements)

References 54 publications

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“…After being mixed continuously for 30 min, the nanoarchitecture-attached exosomes were separated using a bar magnet, as shown in Figure 4 C. After that, we also used the human PD-L1 enzyme-linked immunoassay kit for the quantitation of the PD-L1 (+) exosomes. 13 − 17 The eperimental ELISA results are very similar to those we obtained by differential centrifugation. After magnetic separation, using the ELISA data, we found that the percentage of PD-L1 (+) exosomes is around five-times higher for non-small-cell lung cancer H460 cells lines than for A549 lung cancer cells lines.…”

Section: Resultssupporting

confidence: 84%

“… 8 − 16 Due to the above fact, evaluating the presence of exosomal PD-L1 is very important to determine the immune escape and tumor progression. 12 − 17 …”

Section: Introductionmentioning

confidence: 99%

“… 12 − 22 Several clinical studies indicate that exosome-carrying PD-L1 can be associated with a suppression of the antitumor immune response for NSCLC. 10 − 17 As a result, analyzing the PD-L1 expression exosomes in the tumor microenvironment is very important for the clinical success of lung cancer treatment. 12 − 17 Since biological fluids containing exosomes also have cell debris, proteins, different types of other vesicles, and several biologically important molecules, as we and others have reported before, isolation and enrichment steps are the initial steps to separate an exosome before it can be analyzed.…”

Section: Introductionmentioning

confidence: 99%

“… 10 − 17 As a result, analyzing the PD-L1 expression exosomes in the tumor microenvironment is very important for the clinical success of lung cancer treatment. 12 − 17 Since biological fluids containing exosomes also have cell debris, proteins, different types of other vesicles, and several biologically important molecules, as we and others have reported before, isolation and enrichment steps are the initial steps to separate an exosome before it can be analyzed. 12 − 22 For this purpose, we have designed an immunomagnetic nanoarchitecture that can be used to isolate the PD-L1-positive (PD-L1 (+)) exosome from the cell culture and a whole-blood sample.…”

Section: Introductionmentioning

confidence: 99%

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Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes

et al. 2022

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As per the American Cancer Society, lung cancer is the leading cause of cancer-related death worldwide. Since the accumulation of exosomal programmed cell death ligand 1 (PD-L1) is associated with therapeutic resistance in programmed cell death 1 (PD-1) and PD-L1 immunotherapy, tracking PD-L1-positive (PD-L1 (+)) exosomes is very important for predicting anti-PD-1 and anti-PD-L1 therapy for lung cancer. Herein, we report the design of an anti-PD-L1 monoclonal antibody-conjugated magnetic-nanoparticle-attached yellow fluorescent carbon dot (YFCD) based magnetic-fluorescence nanoarchitecture for the selective separation and accurate identification of PD-L1-expressing exosomes. In this work, photostable YFCDs with a good photoluminescence quantum yield (23%) were synthesized by hydrothermal treatment. In addition, nanoarchitectures with superparamagnetic (28.6 emu/g), biocompatible, and selective bioimaging capabilities were developed by chemically conjugating the anti-PD-L1 antibody and YFCDs with iron oxide nanoparticles. Importantly, using human non-small-cell lung cancer H460 cells lines, which express a high amount of PD-L1 (+) exosomes, A549 lung cancer cells lines, which express a low amount of PD-L1 (+) exosomes, and the normal skin HaCaT cell line, which does not express any PD-L1 (+) exosomes, we demonstrate that nanoarchitectures are capable of effectively separating and tracking PD-L1-positive exosomes simultaneously. Furthermore, as a proof-of-concept of clinical setting applications, a whole blood sample infected with PD-L1 (+) exosomes was analyzed, and our finding shows that this nanoarchitecture holds great promise for clinical applications.

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Section: Resultssupporting

confidence: 84%

“… 8 − 16 Due to the above fact, evaluating the presence of exosomal PD-L1 is very important to determine the immune escape and tumor progression. 12 − 17 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes

et al. 2022

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“…Additionally, a new PD-L1 aptamer, which not only has good selectivity but also interacts with natural PD-L1 more efficiently than antibodies, was combined with thermophoresis to yield a uniform, low volume, efficient, and sensitive method for the quantitation of Exo-PD-L1 (HOLMES-ExoPD-L1) [ 149 ]. Wang et al used gold-silver (Au@Ag) core–shell nanobipyramids and gold nanorods to produce a unique plasma signal pattern, allowing rapid and highly sensitive exosome detection and accurate identification of Exo-PD-L1 [ 150 ].…”

Section: Potential Application Of Ev Pd-l1 In Tumorsmentioning

confidence: 99%

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

et al. 2022

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Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets.

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Dielectrophoretic Capture of Cancer‐Derived Small‐Extracellular‐Vesicle‐Bound Janus Nanoparticles via Lectin–Glycan Interaction

Choi,

Akyildiz,

Seong

et al. 2023

Adv Healthcare Materials

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Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell‐derived small extracellular vesicles (PC‐sEVs) based on lectin–glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC‐sEVs in a dielectrophoretic (DEP) system. PC‐sEVs are selectively bound to the lectin‐conjugated Janus nanoparticles (lectin–JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19‐9 (CA19‐9) antibodies. Furthermore, sEVs‐bound Lectin–JNPs (sEVs‐Lec‐JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs–Lec–JNP on the electrodes. Their results, which are confirmed by lectin–JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC‐sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.

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Nanoplasmonic Sandwich Immunoassay for Tumor-Derived Exosome Detection and Exosomal PD-L1 Profiling

Cited by 39 publications

References 54 publications

Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes

Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

Dielectrophoretic Capture of Cancer‐Derived Small‐Extracellular‐Vesicle‐Bound Janus Nanoparticles via Lectin–Glycan Interaction

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