Stimuli-responsive polypeptide nanogels for trypsin inhibition

0558480 - ÚMCH 2023 RIV DE eng J - Článek v odborném periodiku
Šálek, Petr - Dvořáková, Jana - Hladysh, Sviatoslav - Oleshchuk, Diana - Pavlova, Ewa - Kučka, Jan - Proks, Vladimír
Stimuli-responsive polypeptide nanogels for trypsin inhibition.
Beilstein Journal of Nanotechnology. Roč. 13, 22 Jun (2022), s. 538-548. ISSN 2190-4286. E-ISSN 2190-4286
Grant CEP: GA ČR(CZ) GA21-06524S; GA MŠMT(CZ) LM2018133
Institucionální podpora: RVO:61389013
Klíčová slova: α1-antitrypsin * inflammatory mediator * nanogel
Obor OECD: Polymer science
Impakt faktor: 3.1, rok: 2022
Způsob publikování: Open access
https://www.beilstein-journals.org/bjnano/articles/13/45

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.
Trvalý link: https://hdl.handle.net/11104/0332814