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Stimuli-responsive polypeptide nanogels for trypsin inhibition
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SYSNO ASEP 0558480 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Stimuli-responsive polypeptide nanogels for trypsin inhibition Author(s) Šálek, Petr (UMCH-V) RID, ORCID
Dvořáková, Jana (UMCH-V) RID, ORCID
Hladysh, Sviatoslav (UMCH-V) RID, ORCID
Oleshchuk, Diana (UMCH-V) ORCID
Pavlova, Ewa (UMCH-V) RID
Kučka, Jan (UMCH-V) RID, ORCID
Proks, Vladimír (UMCH-V) RID, ORCIDSource Title Beilstein Journal of Nanotechnology. - : Beilstein - Institut zur Foerderung der Chemischen Wissenschaften - ISSN 2190-4286
Roč. 13, 22 Jun (2022), s. 538-548Number of pages 11 s. Language eng - English Country DE - Germany Keywords α1-antitrypsin ; inflammatory mediator ; nanogel Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects GA21-06524S GA ČR - Czech Science Foundation (CSF) LM2018133 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMCH-V - RVO:61389013 UT WOS 000820226200001 EID SCOPUS 85134383301 DOI 10.3762/bjnano.13.45 Annotation A new type of hydrophilic, biocompatible, and biodegradable polypeptide nanogel depots loaded with the natural serine protease inhibitor α1-antitrypsin (AAT) was applied for the inhibition of the inflammatory mediator trypsin. Two types of nanogels were prepared from linear synthetic polypeptides based on biocompatible and biodegradable poly[N5-(2-hydroxyethyl)-ʟ-glutamine-ran-N5-propargyl-ʟ-glutamine-ran-N5-(6-aminohexyl)-ʟ-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-ʟ-glutamine] (PHEG-Tyr) or biocompatible Nα-ʟ-lysine-grafted α,β-poly[(2-propyne)-ᴅ,ʟ-aspartamide-ran-(2-hydroxyethyl)-ᴅʟ-aspartamide-ran-(2-(4-hydroxyphenyl)ethyl)-ᴅʟ-aspartamide] (Nα-Lys-NG). Both nanogels were prepared by HRP/H2O2-mediated crosslinking in inverse miniemulsions with pH and temperature-stimuli responsive behavior confirmed by dynamic light scattering and zeta potential measurements. The loading capacity of PHEG-Tyr and Nα-Lys-NG nanogels and their release profiles were first optimized with bovine serum albumin. The nanogels were then used for loading and release of AAT. PHEG-Tyr and Nα-Lys-NG nanogels showed different loading capacities for AAT with the maximum (20%) achieved with Nα-Lys-NG nanogel. In both cases, the nanogel depots demonstrated a burst release of AAT during the first 6 h, which could be favorable for quick inhibition of trypsin. A consequent pilot in vitro inhibition study revealed that both PHEG-Tyr and Nα-Lys-NG nanogels loaded with AAT successfully inhibited the enzymatic activity of trypsin. Furthermore, the inhibitory efficiency of the AAT-loaded nanogels was higher than that of only AAT. Interestingly, also non-loaded PHEG-Tyr and Nα-Lys-NG nanogels were shown to effectively inhibit trypsin because they contain suitable amino acids in their structures that effectively block the active site of trypsin. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2023 Electronic address https://www.beilstein-journals.org/bjnano/articles/13/45
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