Histidine-modified UiO-66(Zr) nanoparticles as an effective pH-responsive carrier for 5-fluorouracil drug delivery system: A possible pathway to more effective brain cancer treatments

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17310%2F25%3AA2603C0J" target="_blank" >RIV/61988987:17310/25:A2603C0J - isvavai.cz</a>

Výsledek na webu

<a href="https://linkinghub.elsevier.com/retrieve/pii/S1385894725086978" target="_blank" >https://linkinghub.elsevier.com/retrieve/pii/S1385894725086978</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cej.2025.167857" target="_blank" >10.1016/j.cej.2025.167857</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Histidine-modified UiO-66(Zr) nanoparticles as an effective pH-responsive carrier for 5-fluorouracil drug delivery system: A possible pathway to more effective brain cancer treatments

Popis výsledku v původním jazyce

The development of pH-responsive drug delivery systems is crucial for improving the targeted release of chemotherapeutics in tumour microenvironments. In this study, UiO-66(Zr)-NH₂ and its post-synthetically histidine(His)-modified form, UiO-66(Zr)-His, were investigated as potential carriers for 5-fluorouracil (5FU). His functionalisation was achieved through amide bond formation, with a binding efficiency of 62 %. The encapsulationefficiency of 5FU reached 137.1 mg g− 1 for UiO-66(Zr)-NH₂ and 45.0 mg g− 1 for UiO-66(Zr)-His, demonstratingthe impact of surface modifications on drug loading capacity. Drug release studies at 37 ◦C under different pHconditions (2.0, 5.5, and 7.4) confirmed the pH-responsive behaviour of both materials. The maximum drugrelease after 10 h was 68 % at pH = 2, 71 % at pH = 5.5, and 81 % at pH = 7.4 for UiO-66(Zr)-NH₂, whereas UiO66(Zr)-His exhibited enhanced release at mildly acidic conditions (88 % at pH = 5.5). Kinetic modelling revealedthat the Weibull and Higuchi models provided the best fit (R2 > 0.9), confirming diffusion-controlled release. Thehigh biocompatibility of the prepared materials was investigated in vitro on dermal fibroblasts and in vivo on thepreclinical quail embryonic model of the chorioallantoic membrane as healthy tissue. The endocytotic pathwaywas identified as the main route for the entry of aminated nanoparticles and modified with His. Autophagyconfirmed by Western blot and electron microscopy, protected fibroblasts before 5FU bioactivity. Finally, thebiological activity of 5FU transported by UiO-66(Zr)-NH2 and UiO-66(Zr)-His was investigated in 2D and 3Dmodels of glioblastoma U87MG (brain cancer) cells in spheroids. Fluorescence imaging revealed efficient cellularuptake and cytotoxic effects, particularly for UiO-66(Zr)-His+5FU, which showed enhanced colocalisation withlysosomes and crosstalk with mitochondria. Administration of UiO-66(Zr)-His+5FU to U87MG cells resulted in asignificant increase in lactate dehydrogenase production and reduction in the formation of 3D spheroids. Thesefindings highlight UiO-66(Zr)-His as a promising candidate for fluorescence-based photodiagnostics and pH- responsive chemotherapy, especially by reducing their size in the treatment of brain tumours where themicroenvironment is slightly acidic (pH = 5.9–6.9).

Název v anglickém jazyce

Histidine-modified UiO-66(Zr) nanoparticles as an effective pH-responsive carrier for 5-fluorouracil drug delivery system: A possible pathway to more effective brain cancer treatments

Popis výsledku anglicky

The development of pH-responsive drug delivery systems is crucial for improving the targeted release of chemotherapeutics in tumour microenvironments. In this study, UiO-66(Zr)-NH₂ and its post-synthetically histidine(His)-modified form, UiO-66(Zr)-His, were investigated as potential carriers for 5-fluorouracil (5FU). His functionalisation was achieved through amide bond formation, with a binding efficiency of 62 %. The encapsulationefficiency of 5FU reached 137.1 mg g− 1 for UiO-66(Zr)-NH₂ and 45.0 mg g− 1 for UiO-66(Zr)-His, demonstratingthe impact of surface modifications on drug loading capacity. Drug release studies at 37 ◦C under different pHconditions (2.0, 5.5, and 7.4) confirmed the pH-responsive behaviour of both materials. The maximum drugrelease after 10 h was 68 % at pH = 2, 71 % at pH = 5.5, and 81 % at pH = 7.4 for UiO-66(Zr)-NH₂, whereas UiO66(Zr)-His exhibited enhanced release at mildly acidic conditions (88 % at pH = 5.5). Kinetic modelling revealedthat the Weibull and Higuchi models provided the best fit (R2 > 0.9), confirming diffusion-controlled release. Thehigh biocompatibility of the prepared materials was investigated in vitro on dermal fibroblasts and in vivo on thepreclinical quail embryonic model of the chorioallantoic membrane as healthy tissue. The endocytotic pathwaywas identified as the main route for the entry of aminated nanoparticles and modified with His. Autophagyconfirmed by Western blot and electron microscopy, protected fibroblasts before 5FU bioactivity. Finally, thebiological activity of 5FU transported by UiO-66(Zr)-NH2 and UiO-66(Zr)-His was investigated in 2D and 3Dmodels of glioblastoma U87MG (brain cancer) cells in spheroids. Fluorescence imaging revealed efficient cellularuptake and cytotoxic effects, particularly for UiO-66(Zr)-His+5FU, which showed enhanced colocalisation withlysosomes and crosstalk with mitochondria. Administration of UiO-66(Zr)-His+5FU to U87MG cells resulted in asignificant increase in lactate dehydrogenase production and reduction in the formation of 3D spheroids. Thesefindings highlight UiO-66(Zr)-His as a promising candidate for fluorescence-based photodiagnostics and pH- responsive chemotherapy, especially by reducing their size in the treatment of brain tumours where themicroenvironment is slightly acidic (pH = 5.9–6.9).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20400 - Chemical engineering

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Chemical Engineering Journal

ISSN

1385-8947

e-ISSN

1873-3212

Svazek periodika

—

Číslo periodika v rámci svazku

15 October

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

27

Strana od-do

—

Kód UT WoS článku

001568896600027

EID výsledku v databázi Scopus

2-s2.0-105014630145