Preparation of lactic acid- and glucose-responsive poly(epsilon-caprolactone)-b-poly(ethylene oxide) block copolymer micelles using phenylboronic ester as a sensitive block linkage

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10386218" target="_blank" >RIV/00216208:11310/18:10386218 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1039/c7nr09427b" target="_blank" >https://doi.org/10.1039/c7nr09427b</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c7nr09427b" target="_blank" >10.1039/c7nr09427b</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Preparation of lactic acid- and glucose-responsive poly(epsilon-caprolactone)-b-poly(ethylene oxide) block copolymer micelles using phenylboronic ester as a sensitive block linkage

Popis výsledku v původním jazyce

The present study describes the synthesis, self-assembly and responsiveness to glucose and lactic acid of biocompatible and biodegradable block copolymer micelles using phenylboronic ester as the linkage between hydrophobic poly(epsilon-caprolactone) (PCL) and hydrophilic poly(ethylene oxide) (PEO). The PCL block with pendant phenylboronic acid (PCLBA) was synthesized by combining epsilon-caprolactone (epsilon-CL) ring-opening polymerisation (ROP), using 4-hydroxymethyl(phenylboronic) acid pinacolate as the initiator, and pinacol deprotection. The glucose-terminated PEO (PEOGlc) was prepared by 1,3-dipolar, Cu(I)-catalysed, alkyne-azide cycloaddition of alpha-methoxy-omega-propargyl poly(ethylene oxide) and 1-azido-1-deoxy-D-glucopyranose. All new compounds were evaluated by H-1 NMR spectroscopy and by SEC analysis. PCLBA and PEOGlc blocks were linked in NaOH acetone solution, which was indirectly confirmed by Alizarin Red S fluorescence and directly by H-1 NMR spectroscopy. Dialysis against Milli-Q water induced the self-assembly of PCLBA-b-PEOGlc nanoparticles, which were characterised by static (SLS) and dynamic (DLS) light scattering and by cryogenic transmission electron microscopy (cryo-TEM). Furthermore, the microscopic properties of the charged interface between the hydrophobic PCLBA core and the hydrophilic PEOGlc shell were examined by electrophoretic light scattering (zeta potential) and by fluorescence spectroscopy using the fluorescent probe 5-(N-dodecanoyl)aminofluorescein (DAF) as a pH indicator. Subsequently, the nanoparticles were transferred to a phosphate buffer saline (PBS) solution supplemented with different concentrations of glucose to simulate the physiological conditions in blood or lactic acid to simulate acidic cytosolic or endosomal conditions in tumour cells. Adding a surplus of glucose or lactic acid, which competitively binds to PBA, removes the stabilising hydrophilic PEOGlc blocks, thereby triggering marked nanoparticle aggregation. However, the rate of aggregation induced by lactic acid is considerably faster than that induced by glucose, as confirmed by light scattering. Thus, this novel block copolymer may contribute to the field of selective, lactic acid-and/or glucose-responsive drug delivery vehicle design under both pathological and physiological conditions.

Název v anglickém jazyce

Preparation of lactic acid- and glucose-responsive poly(epsilon-caprolactone)-b-poly(ethylene oxide) block copolymer micelles using phenylboronic ester as a sensitive block linkage

Popis výsledku anglicky

The present study describes the synthesis, self-assembly and responsiveness to glucose and lactic acid of biocompatible and biodegradable block copolymer micelles using phenylboronic ester as the linkage between hydrophobic poly(epsilon-caprolactone) (PCL) and hydrophilic poly(ethylene oxide) (PEO). The PCL block with pendant phenylboronic acid (PCLBA) was synthesized by combining epsilon-caprolactone (epsilon-CL) ring-opening polymerisation (ROP), using 4-hydroxymethyl(phenylboronic) acid pinacolate as the initiator, and pinacol deprotection. The glucose-terminated PEO (PEOGlc) was prepared by 1,3-dipolar, Cu(I)-catalysed, alkyne-azide cycloaddition of alpha-methoxy-omega-propargyl poly(ethylene oxide) and 1-azido-1-deoxy-D-glucopyranose. All new compounds were evaluated by H-1 NMR spectroscopy and by SEC analysis. PCLBA and PEOGlc blocks were linked in NaOH acetone solution, which was indirectly confirmed by Alizarin Red S fluorescence and directly by H-1 NMR spectroscopy. Dialysis against Milli-Q water induced the self-assembly of PCLBA-b-PEOGlc nanoparticles, which were characterised by static (SLS) and dynamic (DLS) light scattering and by cryogenic transmission electron microscopy (cryo-TEM). Furthermore, the microscopic properties of the charged interface between the hydrophobic PCLBA core and the hydrophilic PEOGlc shell were examined by electrophoretic light scattering (zeta potential) and by fluorescence spectroscopy using the fluorescent probe 5-(N-dodecanoyl)aminofluorescein (DAF) as a pH indicator. Subsequently, the nanoparticles were transferred to a phosphate buffer saline (PBS) solution supplemented with different concentrations of glucose to simulate the physiological conditions in blood or lactic acid to simulate acidic cytosolic or endosomal conditions in tumour cells. Adding a surplus of glucose or lactic acid, which competitively binds to PBA, removes the stabilising hydrophilic PEOGlc blocks, thereby triggering marked nanoparticle aggregation. However, the rate of aggregation induced by lactic acid is considerably faster than that induced by glucose, as confirmed by light scattering. Thus, this novel block copolymer may contribute to the field of selective, lactic acid-and/or glucose-responsive drug delivery vehicle design under both pathological and physiological conditions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GJ17-00289Y" target="_blank" >GJ17-00289Y: Multikompartmentalizované nanostruktury citlivé na sacharidy a pH pro duální solubilizaci a uvolňování léčiv</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nanoscale

ISSN

2040-3364

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

8428-8442

Kód UT WoS článku

000432096400011

EID výsledku v databázi Scopus

2-s2.0-85046894546