Fluorophore labeling of core-crosslinked polymeric micelles for multimodal in vivo and ex vivo optical imaging

Author:

Shi Yang1,Kunjachan Sijumon2,Wu Zhuojun234,Gremse Felix2,Moeckel Diana2,van Zandvoort Marc34,Kiessling Fabian2,Storm Gert15,van Nostrum Cornelus F1,Hennink Wim E1,Lammers Twan125

Affiliation:

1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands

2. Department of Experimental Molecular Imaging (ExMI), Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Clinic, Aachen, Germany

3. Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Clinic, Aachen, Germany

4. Department of Genetics & Cell Biology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

5. Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente, Enschede, The Netherlands

Abstract

Aim: To enable multimodal in vivo and ex vivo optical imaging of the biodistribution and tumor accumulation of core-crosslinked polymeric micelles (CCPMs). Materials & methods: mPEG-b-p(HPMAm-Lac)-based polymeric micelles, core-crosslinked via cystamine and covalently labeled with two different fluorophores (Dy-676/488), were synthesized. The CCPMs were intravenously injected into CT26 tumor-bearing mice. Results: Upon intravenous injection, the CCPMs accumulated in CT26 tumors reasonably efficiently, with values reaching approximately 4%ID at 24 h. Ex vivo two-photon laser scanning microscopy confirmed efficient extravasation of the image-guided CCPMs out of tumor blood vessels and relatively deep penetration into the tumor interstitium. Conclusion: CCPMs were labeled with multiple fluorophores, and the results obtained exemplify that combining several different in vivo and ex vivo optical imaging techniques is highly useful for analyzing the biodistribution and tumor accumulation of nanomedicines.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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