Stimuli-responsive multifunctional micelles of ABC vs. ACB triblock terpolymers using reversible covalent bonding of phenylboronic acid: controlled synthesis, self-assembly and model drug release

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F21%3A10431791" target="_blank" >RIV/00216208:11310/21:10431791 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YHAXjOQ4Op" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YHAXjOQ4Op</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molliq.2021.116528" target="_blank" >10.1016/j.molliq.2021.116528</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Stimuli-responsive multifunctional micelles of ABC vs. ACB triblock terpolymers using reversible covalent bonding of phenylboronic acid: controlled synthesis, self-assembly and model drug release

Popis výsledku v původním jazyce

We report the synthesis and self-assembly of well-defined, amphiphilic, biodegradable and glucose- and pH-responsive ABC and ACB triblock terpolymer multifunctional micelles in aqueous media using blocks consisting of poly(ethylene oxide) (PEO), poly(epsilon-caprolactone) (PCL), and boronic acid-functionalised poly (epsilon-caprolactone) (PBA). The terpolymers were synthesized by sequential ring-opening polymerisation (ROP) and functionalised using phenylboronic acid pinacolate via alkyne - azide cycloaddition (CuAAC). Lastly, the pinacole groups were deprotected by mild acidic catalysis to introduce phenylboronic acid for controlled drug solubilisation and delivery. ABC and ACB triblock terpolymers self-assembled into various multifunctional micelles in aqueous media depending on the state of the phenylboronic acid (pinacol protected, BAPin vs. deprotected, BA) and on the preparation procedure, as shown by dynamic and static light scattering (DLS and SLS) and by cryogenic transmission electron microscopy (cryo-TEM). The fluorescence probe Alizarin Red S (ARS) was used as a model drug, which covalently binds to BA, and its uptake was monitored by fluorescence spectroscopy and high-performance liquid chromatography (HPLC). When adding a surplus of glucose, which competitively binds to BA, ARS was released as a function of micelle morphology (core-shell corona (ABC) vs. mixed-shell (ACB) micelles). When transferring ARS-loaded nanoparticles to phosphate buffer saline (PBS) solutions at different pH values (7.4 and 5 or 3) simulating physiological and tumour conditions, respectively, ABC micelles released ARS only at low pH, while ACB micelles released ARS in response to glucose and to both low and physiological pH values. Therefore, in this system, ABC micelles are better suited for drug delivery to tumour cells than their ACB counterparts because they retain their cargo in PBS at high glucose concentrations but release it under acidic conditions, which occur in hypoxic cancer cells, thus highlighting the potential of ABC micelles for targeted drug delivery in the context of cancer therapy.

Název v anglickém jazyce

Stimuli-responsive multifunctional micelles of ABC vs. ACB triblock terpolymers using reversible covalent bonding of phenylboronic acid: controlled synthesis, self-assembly and model drug release

Popis výsledku anglicky

We report the synthesis and self-assembly of well-defined, amphiphilic, biodegradable and glucose- and pH-responsive ABC and ACB triblock terpolymer multifunctional micelles in aqueous media using blocks consisting of poly(ethylene oxide) (PEO), poly(epsilon-caprolactone) (PCL), and boronic acid-functionalised poly (epsilon-caprolactone) (PBA). The terpolymers were synthesized by sequential ring-opening polymerisation (ROP) and functionalised using phenylboronic acid pinacolate via alkyne - azide cycloaddition (CuAAC). Lastly, the pinacole groups were deprotected by mild acidic catalysis to introduce phenylboronic acid for controlled drug solubilisation and delivery. ABC and ACB triblock terpolymers self-assembled into various multifunctional micelles in aqueous media depending on the state of the phenylboronic acid (pinacol protected, BAPin vs. deprotected, BA) and on the preparation procedure, as shown by dynamic and static light scattering (DLS and SLS) and by cryogenic transmission electron microscopy (cryo-TEM). The fluorescence probe Alizarin Red S (ARS) was used as a model drug, which covalently binds to BA, and its uptake was monitored by fluorescence spectroscopy and high-performance liquid chromatography (HPLC). When adding a surplus of glucose, which competitively binds to BA, ARS was released as a function of micelle morphology (core-shell corona (ABC) vs. mixed-shell (ACB) micelles). When transferring ARS-loaded nanoparticles to phosphate buffer saline (PBS) solutions at different pH values (7.4 and 5 or 3) simulating physiological and tumour conditions, respectively, ABC micelles released ARS only at low pH, while ACB micelles released ARS in response to glucose and to both low and physiological pH values. Therefore, in this system, ABC micelles are better suited for drug delivery to tumour cells than their ACB counterparts because they retain their cargo in PBS at high glucose concentrations but release it under acidic conditions, which occur in hypoxic cancer cells, thus highlighting the potential of ABC micelles for targeted drug delivery in the context of cancer therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/LTAIN19078" target="_blank" >LTAIN19078: Nanostrukturované micely s jedním či více kompartmenty a odezvou na vnější podněty tvořené blokovými kopolymery: Materiály a aplikace</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Liquids

ISSN

0167-7322

e-ISSN

—

Svazek periodika

335

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

116528

Kód UT WoS článku

000662831600121

EID výsledku v databázi Scopus

2-s2.0-85107120951