Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F25%3A00636795" target="_blank" >RIV/61389013:_____/25:00636795 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S305056232500042X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S305056232500042X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celbio.2025.100051" target="_blank" >10.1016/j.celbio.2025.100051</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Popis výsledku v původním jazyce

Inflammation is a hallmark of cancer. It contributes to a heterogeneous, hyperpermeable, and poorly perfused tumor vasculature, as well as to a dense and disorganized extracellular matrix, which together negatively affect drug delivery. Reasoning that glucocorticoids have pleiotropic effects, we use clinical-stage dexamethasone liposomes (LipoDex) to prime the tumor microenvironment for improved drug delivery and enhanced treatment efficacy. We show that LipoDex priming improves tumor vascular function and reduces extracellular matrix deposition. Single-cell sequencing corroborates LipoDex-mediated inhibition of pro-inflammatory, pro-angiogenic, and pro-fibrogenic gene expression in mononuclear cells, tumor-associated macrophages, and cancer-associated fibroblasts. Multimodal optical imaging illustrates that LipoDex pre-treatment increases the tumor accumulation and intratumoral distribution of subsequently administered polymeric and liposomal drug delivery systems. Using Doxil as a prototypic nanodrug, we finally show that LipoDex priming promotes antitumor treatment efficacy. Altogether, our findings demonstrate that desmoplastic tumors can be primed for improved drug targeting and therapy using clinical-stage glucocorticoid liposomes.

Název v anglickém jazyce

Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Popis výsledku anglicky

Inflammation is a hallmark of cancer. It contributes to a heterogeneous, hyperpermeable, and poorly perfused tumor vasculature, as well as to a dense and disorganized extracellular matrix, which together negatively affect drug delivery. Reasoning that glucocorticoids have pleiotropic effects, we use clinical-stage dexamethasone liposomes (LipoDex) to prime the tumor microenvironment for improved drug delivery and enhanced treatment efficacy. We show that LipoDex priming improves tumor vascular function and reduces extracellular matrix deposition. Single-cell sequencing corroborates LipoDex-mediated inhibition of pro-inflammatory, pro-angiogenic, and pro-fibrogenic gene expression in mononuclear cells, tumor-associated macrophages, and cancer-associated fibroblasts. Multimodal optical imaging illustrates that LipoDex pre-treatment increases the tumor accumulation and intratumoral distribution of subsequently administered polymeric and liposomal drug delivery systems. Using Doxil as a prototypic nanodrug, we finally show that LipoDex priming promotes antitumor treatment efficacy. Altogether, our findings demonstrate that desmoplastic tumors can be primed for improved drug targeting and therapy using clinical-stage glucocorticoid liposomes.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

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

Cell Biomaterials

ISSN

3050-5623

e-ISSN

—

Svazek periodika

1

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

100051

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-105020060857