Effect of cellular and microenvironmental multidrug resistance on tumor-targeted drug delivery in triple-negative breast cancer

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F23%3A00567637" target="_blank" >RIV/61389013:_____/23:00567637 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0168365922008707?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365922008707?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2022.12.056" target="_blank" >10.1016/j.jconrel.2022.12.056</a>

Result language

angličtina

Original language name

Effect of cellular and microenvironmental multidrug resistance on tumor-targeted drug delivery in triple-negative breast cancer

Original language description

Multidrug resistance (MDR) reduces the efficacy of chemotherapy. Besides inducing the expression of drug efflux pumps, chemotherapy treatment alters the composition of the tumor microenvironment (TME), thereby potentially limiting tumor-directed drug delivery. To study the impact of MDR signaling in cancer cells on TME remodeling and nanomedicine delivery, we generated multidrug-resistant 4T1 triple-negative breast cancer (TNBC) cells by exposing sensitive 4T1 cells to gradually increasing doxorubicin concentrations. In 2D and 3D cell cultures, resistant 4T1 cells are presented with a more mesenchymal phenotype and produced increased amounts of collagen. While sensitive and resistant 4T1 cells showed similar tumor growth kinetics in vivo, the TME of resistant tumors was enriched in collagen and fibronectin. Vascular perfusion was also significantly increased. Fluorophore-labeled polymeric (∼10 nm) and liposomal (∼100 nm) drug carriers were administered to mice with resistant and sensitive tumors. Their tumor accumulation and penetration were studied using multimodal and multiscale optical imaging. At the whole tumor level, polymers accumulate more efficiently in resistant than in sensitive tumors. For liposomes, the trend was similar, but the differences in tumor accumulation were insignificant. At the individual blood vessel level, both polymers and liposomes were less able to extravasate out of the vasculature and penetrate the interstitium in resistant tumors. In a final in vivo efficacy study, we observed a stronger inhibitory effect of cellular and microenvironmental MDR on liposomal doxorubicin performance than free doxorubicin. These results exemplify that besides classical cellular MDR, microenvironmental drug resistance features should be considered when aiming to target and treat multidrug-resistant tumors more efficiently.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10404 - Polymer science

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

1873-4995

Volume of the periodical

354

Issue of the periodical within the volume

February

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

10

Pages from-to

784-793

UT code for WoS article

000961158400001

EID of the result in the Scopus database

2-s2.0-85147190710