A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles

Kangfu Chen; Bill T.V. Duong; Sharif U. Ahmed; Piriththiv Dhavarasa; Zongjie Wang; Mahmoud Labib; Connor Flynn; Jingya Xu; Yi Y. Zhang; Hansen Wang; Xiaolong Yang; Jagotamoy Das; Hossein Zargartalebi; Yuan Ma; Shana O. Kelley

doi:10.1038/s41467-023-41285-8

A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles

Kangfu Chen, Bill T.V. Duong, Sharif U. Ahmed, Piriththiv Dhavarasa, Zongjie Wang, Mahmoud Labib, Connor Flynn, Jingya Xu, Yi Y. Zhang, Hansen Wang, Xiaolong Yang, Jagotamoy Das, Hossein Zargartalebi, Yuan Ma, Shana O. Kelley^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

Original language	English (US)
Article number	5576
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-41285-8
State	Published - Dec 2023

Funding

We would like to acknowledge the cleanroom in St. Michael’s Hospital and the CRAFT cleanroom at the University of Toronto. for providing facilities, materials, and consumables for microfabrication. The reported study is supported by the Nanomedicines Innovation Network (NMIN) of Canada (Project Number: 2019-T3-02 to S.O.K.). We would like to acknowledge the cleanroom in St. Michael’s Hospital and the CRAFT cleanroom at the University of Toronto. for providing facilities, materials, and consumables for microfabrication. The reported study is supported by the Nanomedicines Innovation Network (NMIN) of Canada (Project Number: 2019-T3-02 to S.O.K.).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-023-41285-8

Cite this

Chen, K., Duong, B. T. V., Ahmed, S. U., Dhavarasa, P., Wang, Z., Labib, M., Flynn, C., Xu, J., Zhang, Y. Y., Wang, H., Yang, X., Das, J., Zargartalebi, H., Ma, Y., & Kelley, S. O. (2023). A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles. Nature communications, 14(1), Article 5576. https://doi.org/10.1038/s41467-023-41285-8

@article{1a0106163f694376bd471a2b27232e0d,

title = "A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles",

abstract = "Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.",

author = "Kangfu Chen and Duong, \{Bill T.V.\} and Ahmed, \{Sharif U.\} and Piriththiv Dhavarasa and Zongjie Wang and Mahmoud Labib and Connor Flynn and Jingya Xu and Zhang, \{Yi Y.\} and Hansen Wang and Xiaolong Yang and Jagotamoy Das and Hossein Zargartalebi and Yuan Ma and Kelley, \{Shana O.\}",

note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-41285-8",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles

AU - Chen, Kangfu

AU - Duong, Bill T.V.

AU - Ahmed, Sharif U.

AU - Dhavarasa, Piriththiv

AU - Wang, Zongjie

AU - Labib, Mahmoud

AU - Flynn, Connor

AU - Xu, Jingya

AU - Zhang, Yi Y.

AU - Wang, Hansen

AU - Yang, Xiaolong

AU - Das, Jagotamoy

AU - Zargartalebi, Hossein

AU - Ma, Yuan

AU - Kelley, Shana O.

PY - 2023/12

Y1 - 2023/12

N2 - Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

AB - Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

UR - http://www.scopus.com/inward/record.url?scp=85170379029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85170379029&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-41285-8

DO - 10.1038/s41467-023-41285-8

M3 - Article

C2 - 37696888

AN - SCOPUS:85170379029

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5576

ER -

A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this