CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F24%3A00579339" target="_blank" >RIV/61389013:_____/24:00579339 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0168365923007617?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365923007617?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2023.11.044" target="_blank" >10.1016/j.jconrel.2023.11.044</a>

Result language

angličtina

Original language name

CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy

Original language description

Blood vessel functionality is crucial for efficient tumor-targeted drug delivery. Heterogeneous distribution and perfusion of angiogenic blood vessels contribute to suboptimal accumulation of (nano-) therapeutics in tumors and metastases. To attenuate pathological angiogenesis, an L-RNA aptamer inhibiting the Csingle bondC motif chemokine ligand 2 (CCL2) was administered to mice bearing orthotopic 4T1 triple-negative breast cancer tumors. The effect of CCL2 inhibition on tumor blood vessel functionality and tumor-targeted drug delivery was evaluated via multimodal and multiscale optical imaging, employing fluorophore-labeled polymeric (10 nm) and liposomal (100 nm) nanocarriers. Anti-CCL2 treatment induced a dose-dependent anti-angiogenic effect, reflected by a decreased relative blood volume, increased blood vessel maturity and functionality, and reduced macrophage infiltration, accompanied by a shift in the polarization of tumor-associated macrophages (TAM) towards a less M2-like and more M1-like phenotype. In line with this, CCL2 inhibitor treatment improved the delivery of polymers and liposomes to tumors, and enhanced the antitumor efficacy of free and liposomal doxorubicin. Together, these findings demonstrate that blocking the CCL2-CCR2 axis modulates TAM infiltration and polarization, resulting in vascular normalization and improved tumor-targeted drug delivery.

Czech name

—

Czech description

—

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

<a href="/en/project/NU21-08-00280" target="_blank" >NU21-08-00280: Tumor activatable nanoprobes for highly precise fluorescence-guided surgery</a><br>

Continuities

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

Publication year

2024

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

365

Issue of the periodical within the volume

January

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

358-368

UT code for WoS article

001128439100001

EID of the result in the Scopus database

2-s2.0-85178152924