Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.

Autor: Känkänen V; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland. voitto.kankanen@helsinki.fi.; Department of Applied Physics, School of Science, Aalto University, FI-02150, Espoo, Finland. voitto.kankanen@helsinki.fi., Hirvonen SP; Department of Chemistry, Faculty of Science, University of Helsinki, P. O. Box 55, Helsinki, 00014, Finland., Teesalu T; Laboratory of Precision- and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.; Materials Research Laboratory, University of California, Santa Barbara, CA, 93106, USA., Hirvonen J; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland., Balasubramanian V; Advanced Drug Delivery, Bayer Oy, Turku, FI-20210, Finland. vimalkumar.balasubramanian@bayer.com., Santos HA; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland. h.a.santos@umcg.nl.; Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, Groningen, 9713 AV, The Netherlands. h.a.santos@umcg.nl.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2025 Jan 03. Date of Electronic Publication: 2025 Jan 03.
DOI: 10.1007/s13346-024-01768-7
Abstrakt: Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements. Characterization of NPs with respect to particle size, zeta potential, morphology and peptide content was performed, and their ability to bind to the target protein p32 was tested using a cell-free assay. Importantly, both methods resulted in NPs that were able to bind their target when methyl-terminated PCL-PEG used as the diluent polymer, but not when acid-terminated polymer was used. Moreover, peptide conjugation induced a morphological transformation from spheres to vesicles regardless of the conjugation method used. However, smaller and more homogeneous NPs were obtained by the pre-conjugation method.
Competing Interests: Declarations. Ethics approval and consent to participate: The experiments comply with the current laws of the country in which they were performed. Consent for publication: All authors have read and agreed to the published version of the manuscript. Competing interests: V. Balasubramanian is an employee at Bayer Oy (Finland). V. Känkänen was employed at Bayer Oy (Finland) during a part of this work. Tambet Teesalu is the inventor of a patent related to the linTT1 peptide titled “Targeted delivery system and methods of use therefor” (publication number: 10669311). The other authors declare no other competing financial interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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