cRGD-targeted heparin nanoparticles for effective dual drug treatment of cisplatin-resistant ovarian cancer
Copyright © 2023 Elsevier B.V. All rights reserved..
Resistance to the chemotherapeutic agent cisplatin (DDP) is the primary reason for invalid chemotherapy of ovarian cancer. Given the complex mechanisms underlying chemo-resistance, the design of combination therapies based on blocking multiple mechanisms is a rationale to synergistically elevate therapeutic effect for effectively overcoming cancer chemo-resistance. Herein, we demonstrated a multifunctional nanoparticle (DDP-OlaHR), which could simultaneously co-deliver DDP and Olaparib (Ola, DNA damage repair inhibitor) using targeted ligand cRGD peptide modified with heparin (HR) as nanocarrier, enabling the concurrent tackling of multiple resistance mechanisms to effectively inhibit the growth and metastasis of DDP-resistant ovarian cancer. In combination strategy, heparin could suppress the function of multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) to promote the intracellular accumulation of DDP and Ola by specifically binding with heparanase (HPSE) to down-regulate PI3K/AKT/mTOR signaling pathway, and simultaneously served as a carrier combined with Ola to synergistically enhance the anti-proliferation ability of DDP for resistant ovarian cancer, thus achieving great therapeutic efficacy. Our DDP-Ola@HR could provide a simple and multifunctional combination strategy to trigger an anticipated cascading effect, thus effectively overcoming the chemo-resistance of ovarian cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:356 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 356(2023) vom: 15. Apr., Seite 691-701 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liang, Xiaomei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.09.2023 Date Revised 01.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2023.03.017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354390937 |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Resistance to the chemotherapeutic agent cisplatin (DDP) is the primary reason for invalid chemotherapy of ovarian cancer. Given the complex mechanisms underlying chemo-resistance, the design of combination therapies based on blocking multiple mechanisms is a rationale to synergistically elevate therapeutic effect for effectively overcoming cancer chemo-resistance. Herein, we demonstrated a multifunctional nanoparticle (DDP-OlaHR), which could simultaneously co-deliver DDP and Olaparib (Ola, DNA damage repair inhibitor) using targeted ligand cRGD peptide modified with heparin (HR) as nanocarrier, enabling the concurrent tackling of multiple resistance mechanisms to effectively inhibit the growth and metastasis of DDP-resistant ovarian cancer. In combination strategy, heparin could suppress the function of multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) to promote the intracellular accumulation of DDP and Ola by specifically binding with heparanase (HPSE) to down-regulate PI3K/AKT/mTOR signaling pathway, and simultaneously served as a carrier combined with Ola to synergistically enhance the anti-proliferation ability of DDP for resistant ovarian cancer, thus achieving great therapeutic efficacy. Our DDP-Ola@HR could provide a simple and multifunctional combination strategy to trigger an anticipated cascading effect, thus effectively overcoming the chemo-resistance of ovarian cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ABC-transporter | |
| 650 | 4 | |a Cisplatin | |
| 650 | 4 | |a DNA damage repair | |
| 650 | 4 | |a Heparin-based nanoparticles | |
| 650 | 4 | |a Multiple chemo-resistance mechanisms | |
| 650 | 4 | |a Olaparib | |
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| 700 | 1 | |a Yang, Yulu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chuanqing |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Zhibin |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Wujiang |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jiamao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaoxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Jun-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yifeng |e verfasserin |4 aut | |
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