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Light-Responsive Elastin-Like Peptide-Based Targeted Nanoparticles for Enhanced Spheroid Penetration |
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| Authors: | Dr Duc H T Le Dr Vusala Ibrahimova Sebastian A H van den Wildenberg Dr Hanglong Wu Alba Fonseca Prof?Dr Tomas Torres Dr Elisabeth Garanger Dr William P J Leenders Prof?Dr Roland Brock Prof?Dr Sébastien Lecommandoux Prof?Dr Jan C M van Hest |
| Institution: | 1. Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
Department of Medical BioScience, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands;2. Université Bordeaux, CNRS, Bordeaux INP, LCPO, UMR 5629, 33600 Pessac, France;3. Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands;4. Departamento de Química Orgánica and Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid, 28049 Madrid, Spain;5. Department of Medical BioScience, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands;6. Department of Medical BioScience, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands Department of Medical Biochemistry, College of Medicine, Arabian Gulf University, Manama, 293 Kingdom of Bahrain |
| Abstract: | We describe here a near infrared light-responsive elastin-like peptide (ELP)-based targeted nanoparticle (NP) that can rapidly switch its size from 120 to 25 nm upon photo-irradiation. Interestingly, the targeting function, which is crucial for effective cargo delivery, is preserved after transformation. The NPs are assembled from (targeted) diblock ELP micelles encapsulating photosensitizer TT1-monoblock ELP conjugates. Methionine residues in this monoblock are photo-oxidized by singlet oxygen generated from TT1, turning the ELPs hydrophilic and thus trigger NP dissociation. Phenylalanine residues from the diblocks then interact with TT1 via π-π stacking, inducing the re-formation of smaller NPs. Due to their small size and targeting function, the NPs penetrate deeper in spheroids and kill cancer cells more efficiently compared to the larger ones. This work could contribute to the design of “smart” nanomedicines with deeper penetration capacity for effective anticancer therapies. |
| Keywords: | Elastin-Like Peptides Nanomedicine Photodynamic Therapy Self-Assembly Stimuli-Responsive |