Campus Units

Chemical and Biological Engineering

Document Type

Article

Research Focus Area

Advanced and Nanostructured Materials

Publication Version

Published Version

Publication Date

1-28-2020

Journal or Book Title

ACS Nano

Volume

14

Issue

1

First Page

651

Last Page

663

DOI

10.1021/acsnano.9b07326

Abstract

The overexpression of immunomarker programmed cell death protein 1 (PD-1) and engagement of PD-1 to its ligand, PD-L1, are involved in the functional impairment of cluster of differentiation 8+ (CD8+) T cells, contributing to cancer progression. However, heterogeneities in PD-L1 expression and variabilities in biopsy-based assays render current approaches inaccurate in predicting PD-L1 status. Therefore, PD-L1 screening alone is not predictive of patient response to treatment, which motivates us to simultaneously detect multiple immunomarkers engaged in immune modulation. Here, we have developed multimodal probes, immunoactive gold nanostars (IGNs), that accurately detect PD-L1+ tumor cells and CD8+ T cells simultaneously in vivo, surpassing the limitations of current immunoimaging techniques. IGNs integrate the whole-body imaging of positron emission tomography with high sensitivity and multiplexing of Raman spectroscopy, enabling the dynamic tracking of both immunomarkers. IGNs also monitor response to immunotherapies in mice treated with combinatorial PD-L1 and CD137 agonists and distinguish responders from those nonresponsive to treatment. Our results showed a multifunctional nanoscale probe with capabilities that cannot be achieved with either modality alone, allowing multiplexed immunologic tumor profiling critical for predicting early response to immunotherapies.

Comments

This article is published as Ou, Yu-Chuan, Xiaona Wen, Christopher A. Johnson, Daniel Shae, Oscar D. Ayala, Joseph A. Webb, Eugene C. Lin, ...Rizia Bardhan, et al. "Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies." ACS Nano 14, no. 1 (2020). DOI: 10.1021/acsnano.9b07326.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

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