An Indocyanine Green‐Based Nanoprobe for In Vivo Detection of Cellular Senescence

Author:

Baker Andrew G.12,Hartono Muhamad12,Ou Hui‐Ling1,Popov Andrea Bistrović2,Brown Emma L.34,Joseph James345,Golinska Monika34,González‐Gualda Estela1,Macias David6,Ge Jianfeng1,Denholm Mary1,Morsli Samir1,Sanghera Chandan2,Else Thomas R.34,Greer Heather F.7,Vernet Aude4,Bohndiek Sarah E.34,Muñoz‐Espín Daniel17,Fruk Ljiljana27ORCID

Affiliation:

1. Early Cancer institute Department of Oncology University of Cambridge Hills Road Cambridge CB2 0XZ UK

2. Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK

3. Department of Physics University of Cambridge JJ Thomson Avenue CB3 0HE United Kingdom

4. Cancer Research UK Cambridge Institute Robinson Way Cambridge CB2 0RE UK

5. School of Science and Engineering University of Dundee Dundee DD1 4HN Scotland UK

6. Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocio Universidad de Sevilla Avda.Dr. Fedriani/> Sevilla 41009 Spain

7. Yusuf Hamied Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK

Abstract

AbstractThere is an urgent need to improve conventional cancer‐treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo‐ or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self‐assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.

Funder

Cancer Research UK

Engineering and Physical Sciences Research Council

Royal Society

Publisher

Wiley

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