Multifunctional croconaine nanoparticles for efficient optoacoustic imaging of deep tumors and photothermal therapy

Author:

Liu Nian123,O’Connor Patrick45,Gujrati Vipul12ORCID,Anzenhofer Pia2,Klemm Uwe2,Kleigrewe Karin6,Sattler Michael57ORCID,Plettenburg Oliver48,Ntziachristos Vasilis12

Affiliation:

1. Chair of Biological Imaging, School of Medicine , Technical University of Munich , Munich 81675 , Germany

2. Institute of Biological and Medical Imaging, Helmholtz Zentrum München (GmbH) , Neuherberg 85764 , Germany

3. Department of Nuclear Medicine , PET Center, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310003 , China

4. Institute of Medicinal Chemistry, Helmholtz Zentrum München (GmbH) , Neuherberg 85764 , Germany

5. Institute of Structural Biology, Helmholtz Zentrum München (GmbH) , Neuherberg 85764 , Germany

6. Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS) , Technical University of Munich , Freising 85354 , Germany

7. Bavarian NMR Center and Center for Integrated Protein Science Munich at Department of Chemistry , Technical University of Munich , Garching 85747 , Germany

8. Center for Biomolecular Drug Research (BMWZ) , Institute of Organic Chemistry, Leibniz Universität Hannover , Hannover 30167 , Germany

Abstract

Abstract The proper design of near-infrared light-absorbing agents enables efficient optoacoustic imaging-guided phototherapy. In particular, several croconaine-based organic agents with excellent optical properties have been recently reported for this purpose. However, most of them absorb light below 800 nm, limiting deep-tissue imaging applications. To this end, we utilized a recently described novel croconaine derivative (CR880) to develop CR880-based nanoparticles (CR880-NPs) for effective in vivo delivery, deep tissue optoacoustic imaging and photothermal therapy applications. Radicals and strong ππ stacking in CR880 result in an 880 nm absorption peak with no blue-shift upon condensing to the solid phase. DSPE-PEG2000-formulated CR880-NPs exhibited high optoacoustic generation efficiency and photostability, and could be visualized in the tumors of three different mouse tumor models (breast, brain, and colon tumor) with high image contrast. The high photothermal conversion efficiency of CR880-NPs (∼58%) subsequently enabled efficient in vivo tumor elimination using a low energy laser, while remaining biocompatible and well-tolerated. This work introduces a promising novel agent for cancer theranostics of challenging deep-seated tumors.

Funder

European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation pro-gramme

Publisher

Walter de Gruyter GmbH

Subject

Electrical and Electronic Engineering,Atomic and Molecular Physics, and Optics,Electronic, Optical and Magnetic Materials,Biotechnology

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