TY - JOUR

T1 - Facile Synthesis of a Croconaine-Based Nanoformulation for Optoacoustic Imaging and Photothermal Therapy

AU - Liu, Nian

AU - O'Connor, Patrick

AU - Gujrati, Vipul

AU - Gorpas, Dimitris

AU - Glasl, Sarah

AU - Blutke, Andreas

AU - Walch, Axel

AU - Kleigrewe, Karin

AU - Sattler, Michael

AU - Plettenburg, Oliver

AU - Ntziachristos, Vasilis

N1 - Funding Information: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 694968 (PREMSOT). The research leading to these results was supported by the Deutsche Forschungsgemeinschaft (DFG), Germany (Gottfried Wilhelm Leibniz Prize 2013, NT 3/10?1) as well as by the DFG as part of the CRC 1123 (Z1). N.L. acknowledges support from the China Scholarship Council. Dr. Patrick O'Connor acknowledges support by the Helmholtz Association and the BMBF (16GW0251K). The authors wish to thank Dr. Juan Pablo Fuenzalida Werner for his OGE calculation method, Dr. Juan Antonio Aguilar-Pimentel (German Mouse Clinic/Institute of Experimental Genetics, Helmholtz Zentrum M?nchen) for providing the thermal camera, Dr. Ritu Mishra (TranslaTUM, Technical University of Munich) for supporting confocal imaging experiment, and Dr. Doris Bengel, Uwe Klemm, and Pia Anzenhofer for assisting with experimental procedures. The authors also wish to thank Dr. Sergey Sulima for helpful suggestions on the manuscript. Open access funding enabled and organized by Projekt DEAL.

PY - 2021/5/5

Y1 - 2021/5/5

N2 - 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.

AB - 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.

KW - croconaine

KW - nanoparticles

KW - optoacoustics

KW - photothermal therapy

UR - http://www.scopus.com/inward/record.url?scp=85102650914&partnerID=8YFLogxK

U2 - 10.1002/adhm.202002115

DO - 10.1002/adhm.202002115

M3 - Article

C2 - 33738974

AN - SCOPUS:85102650914

VL - 10

JO - Advanced healthcare materials

JF - Advanced healthcare materials

SN - 2192-2640

IS - 9

M1 - 2002115

ER -