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Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation.
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SYSNO ASEP 0580702 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation. Author(s) Kovář, Marek (MBU-M) RID, ORCID
Šubr, Vladimír (UMCH-V) RID, ORCID
Běhalová, Kateřina (MBU-M)
Studenovský, Martin (UMCH-V) RID, ORCID
Starenko, Daniil (MBU-M)
Kovářová, Jiřina (MBU-M)
Procházková, Petra (MBU-M) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Kostka, Libor (UMCH-V) RID, ORCIDSource Title Nanomedicine: Nanotechnology, Biology and Medicine. - : Elsevier - ISSN 1549-9634
Roč. 56, February 2024 (2024), s. 102730Number of pages 15 s. Language eng - English Country NL - Netherlands Keywords STAT3 inhibitor ; Doxorubicin ; HPMA copolymer carrier ; pH-sensitive drug ; release OECD category Pharmacology and pharmacy R&D Projects NU21-03-00273 GA MZd - Ministry of Health (MZ) LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 38158146 DOI 10.1016/j.nano.2023.102730 Annotation We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1-3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC50 ~0.6-7.9 muM and 0.7-10.9 muM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2025 Electronic address https://www.sciencedirect.com/science/article/pii/S1549963423000813
Number of the records: 1