Light‐Responsive Elastin‐Like Peptide‐Based Targeted Nanoparticles for Enhanced Spheroid Penetration

• Published in: Angewandte Chemie International Edition 2023-06, Vol.62 (24), p.e202300511-n/a
• Main Authors: Le, Duc H. T., Ibrahimova, Vusala, Wildenberg, Sebastian A. H., Wu, Hanglong, Fonseca, Alba, Torres, Tomas, Garanger, Elisabeth, Leenders, William P. J., Brock, Roland, Lecommandoux, Sébastien, Hest, Jan C. M.
• Format: Article
• Language: English
• Subjects: Anticancer properties; Chemical Sciences; Elastin; Elastin - chemistry; Elastin-Like Peptides; Irradiation; Medicinal Chemistry; Methionine; Micelles; Nanomedicine; Nanoparticles; Nanoparticles - chemistry; Peptides - chemistry; Phenylalanine; Photodynamic Therapy; Polymers; Radiation; Residues; Self-Assembly; Singlet oxygen; Spheroids; Stimuli-Responsive
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202300511

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. A near infrared (NIR)‐light‐responsive targeted nanoparticle based on elastin‐like polypeptides and loaded with photosensitizers, is able to transform rapidly into a small nanocluster for enhanced penetration into spheroids. The nanocluster still has its targeting function and thus is highly efficient in both cargo delivery and cell‐killing in photodynamic therapy.