Facile Synthesis of a Croconaine-Based Nanoformulation for Optoacoustic Imaging and Photothermal Therapy

authored by
Nian Liu, Patrick O'Connor, Vipul Gujrati, Dimitris Gorpas, Sarah Glasl, Andreas Blutke, Axel Walch, Karin Kleigrewe, Michael Sattler, Oliver Plettenburg, Vasilis Ntziachristos
Abstract

Near-infrared (NIR) light absorbing theranostic agents can integrate optoacoustic imaging and photothermal therapy for effective personalized precision medicine. However, most of these agents face the challenges of unstable optical properties, material-associated toxicity, and nonbiodegradability, all of which limit their biomedical application. Several croconaine-based organic agents able to overcome some of these limitations have been recently reported, but these suffer from complicated multistep synthesis protocols. Herein, the use of CR760, a croconaine dye with excellent optical properties, is reported for nanoparticle formulation and subsequent optoacoustic imaging and photothermal therapy. Importantly, CR760 can be conveniently prepared in a single step from commercially available materials. Furthermore, CR760 can be covalently attached, via a polyethylene glycol linker, to the αvβ3 integrin ligand c(RGDyC), resulting in self-assembled nanoparticles (NPs) with cancer-targeting capability. Such CR760RGD-NPs exhibit strong NIR absorption, high photostability, high optoacoustic generation efficiency, and active tumor-targeting, making them ideal candidates for optoacoustic imaging. Due to favorable electron transfer, CR760RGD-NPs display a 45.37% photothermal conversion efficiency thereby rendering them additionally useful for photothermal therapy. Targeted tumor elimination, biosafety, and biocompatibility are demonstrated in a 4T1 murine breast tumor model. This work points to the use of CR760RGD-NPs as a promising nanoagent for NIR-based cancer phototheranostics.

Organisation(s)
Institute of Organic Chemistry
External Organisation(s)
Helmholtz Zentrum München - German Research Center for Environmental Health
Technical University of Munich (TUM)
Type
Article
Journal
Advanced healthcare materials
Volume
10
ISSN
2192-2640
Publication date
05.05.2021
Publication status
Published
Peer reviewed
Yes
ASJC Scopus subject areas
Biomaterials, Biomedical Engineering, Pharmaceutical Science
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Electronic version(s)
https://doi.org/10.1002/adhm.202002115 (Access: Open)