Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
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 μM and 0.7-10.9 μM, 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Nanomedicine : nanotechnology, biology, and medicine - 56(2024) vom: 26. Feb., Seite 102730 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kovář, M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.02.2024 Date Revised 06.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.nano.2023.102730 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 μM and 0.7-10.9 μM, 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Doxorubicin | |
| 650 | 4 | |a HPMA copolymer carrier | |
| 650 | 4 | |a STAT3 inhibitor | |
| 650 | 4 | |a pH-sensitive drug release | |
| 650 | 7 | |a hydroxypropyl methacrylate |2 NLM | |
| 650 | 7 | |a UKW89XAX2X |2 NLM | |
| 650 | 7 | |a doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Polymethacrylic Acids |2 NLM | |
| 650 | 7 | |a STAT3 protein, human |2 NLM | |
| 650 | 7 | |a STAT3 Transcription Factor |2 NLM | |
| 650 | 7 | |a Methacrylates |2 NLM | |
| 700 | 1 | |a Šubr, V |e verfasserin |4 aut | |
| 700 | 1 | |a Běhalová, K |e verfasserin |4 aut | |
| 700 | 1 | |a Studenovský, M |e verfasserin |4 aut | |
| 700 | 1 | |a Starenko, D |e verfasserin |4 aut | |
| 700 | 1 | |a Kovářová, J |e verfasserin |4 aut | |
| 700 | 1 | |a Procházková, P |e verfasserin |4 aut | |
| 700 | 1 | |a Etrych, T |e verfasserin |4 aut | |
| 700 | 1 | |a Kostka, L |e verfasserin |4 aut | |
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