Acid-responsive HPMA copolymer-bradykinin conjugate enhances tumor-targeted delivery of nanomedicine

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F21%3A00545461" target="_blank" >RIV/61389013:_____/21:00545461 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0168365921004156?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365921004156?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2021.08.009" target="_blank" >10.1016/j.jconrel.2021.08.009</a>

Result language

angličtina

Original language name

Acid-responsive HPMA copolymer-bradykinin conjugate enhances tumor-targeted delivery of nanomedicine

Original language description

Obstructed blood flow and erratic blood supply in the tumor region attenuate the distribution and accumulation of nanomedicines in the tumor. Therefore, improvement of these conditions is crucial for efficient drug delivery. In this study, we designed and synthesized a novel N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugate of BK, which possessed adequate systemic stability and tumor-selective action required to improve the accumulation of nanomedicines in the tumor. Levulinoyl-BK (Lev-BK) was conjugated to an HPMA-based polymer via an acid-cleavable hydrazone bond (P-BK). An acid-responsive release of Lev-BK from P-BK was observed, and P-BK alone after intradermal application showed below 10% of the BK activity, thus proving a reduction in the vascular permeability activity of BK when attached to the polymer carrier. P-BK pre-treatment improved blood flow in the tumor tissue by 1.4–1.7-fold, which was maintained for more than 4 h. In addition, P-BK pre-treatment increased the tumor accumulation of pegylated liposomal doxorubicin (PLD) by approximately 3-fold. Furthermore, P-BK pre-treatment led to superior antitumor activity of PLD and significantly improved the survival of tumor-bearing mice. The release of BK from P-BK in the acidic milieu of the tumor was a prerequisite for P-BK to exert its effect, as the vascular permeability enhancing activity of P-BK was negligible. Collectively, P-BK pre-treatment improved intratumoral blood flow and augmented tumor accumulation of nanomedicine, thereby resulting in a significant suppression of tumor growth. Therefore, these findings demonstrate that P-BK is a potential concomitant drug for improving the tumor delivery of nanomedicines.

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

<a href="/en/project/GA19-01417S" target="_blank" >GA19-01417S: Tumor-microenvironment responsive nanomedicines as multistage drug delivery systems for experimental therapy of hematologic malignancies</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

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

337

Issue of the periodical within the volume

10 September

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

546-556

UT code for WoS article

000707387900001

EID of the result in the Scopus database

2-s2.0-85113646633