Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 11, Pages 5921-5927Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202015116
Keywords
immunotherapy; fluorescent probes; peptides; polymers; nanoparticles
Categories
Funding
- Nanyang Technological University [M4081627]
- Singapore Ministry of Education [2019-T1-002-045, RG125/19, MOE2018-T2-2-042]
- National Natural Science Foundation of China [81703031, 81672937]
Ask authors/readers for more resources
The development of real-time non-invasive imaging probes for assessing infiltration and activation of cytotoxic T cells (CTLs) is essential for predicting the efficacy of cancer immunotherapy. This study introduces an activatable semiconducting polymer nanoprobe (SPNP) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a CTL activation biomarker, granzyme B. The SPNP can passively target tumors and react with granzyme B in situ to release a dye-labeled peptide, resulting in correlated NIRF and PA signals with the expression level of granzyme B and intratumoral population of CTLs.
Development of real-time non-invasive imaging probes to assess infiltration and activation of cytotoxic T cells (CTLs) is critical to predict the efficacy of cancer immunotherapy, which however remains challenging. Reported here is an activatable semiconducting polymer nanoprobe (SPNP) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a biomarker (granzyme B) associated with activation of CTLs. SPNP comprises a semiconducting polymer (SP) conjugated with a granzyme B cleavable and dye-labeled peptide as the side chain, both of which emit NIRF and PA signals. After systemic administration, SPNP passively targets the tumor and in situ reacts with granzyme B to release the dye-labeled peptide, leading to decreased NIRF and PA signals from the dye but unchanged signals from the polymer. Such ratiometric NIRF and PA signals of SPNP correlate well with the expression level of granzyme B and intratumoral population of CTLs. Thus, this study not only presents the first PA probes for in vivo imaging of immune activation but also provides a molecular design strategy that can be generalized for molecular imaging of other immune-related biomarkers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available