"On/off"-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX
Copyright © 2024 Elsevier Ltd. All rights reserved..
Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PDPTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:307 |
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| Enthalten in: |
Biomaterials - 307(2024) vom: 15. Apr., Seite 122537 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Shuaijun [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biomaterials.2024.122537 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369822048 |
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| 245 | 1 | 0 | |a "On/off"-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX |
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| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PDPTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Improved delivery efficiency | |
| 650 | 4 | |a NSCLC brain metastases | |
| 650 | 4 | |a Restrained adverse reaction | |
| 650 | 4 | |a Switchable crosslinking | |
| 650 | 4 | |a Ultra-pH-sensitive linkages | |
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| 700 | 1 | |a Meng, Caiting |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ruina |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Luyao |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yucheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Sitong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Lou, Chunju |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jinfan |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yifan |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Yanni |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Shengli |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Huafeng |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Zhengtao |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Mingqian |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaobin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hao |e verfasserin |4 aut | |
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