Effect of Cationic Charge Density on Transcytosis of Polyethylenimine
The adsorption-mediated transcytosis (AMT) induced by the electrostatic interaction between the positively charged surface of carriers and negatively charged cell membrane is a new paradigm enabling nanomedicine's tumor extravasation and infiltration. However, little is known about the correlation between the carrier's charge density and its AMT-induced tumor infiltration efficiency. Herein, we investigate the effect of the cationic polymer's charge on the AMT-induced tumor penetration ability using in vitro multilayer tumor spheroids (MTSs). A cationic polymer, polyethylenimine (PEI), is amidized with acetic anhydride to obtain acetylated PEIs (AcPEIs) with different cationic charge densities. As the amidization ratio increases, the AcPEIs' cytotoxicity, zeta potential, and cell-binding affinity significantly decrease. Notably, not only does the weak cell binding (AcPEIs with high acetylation degrees) lead to slow endocytosis and inefficient transcytosis, so does the strong cell-binding PEI. The PEI with 24% acetylation (AcPEI24%) is found to have the highest transcytosis efficiency because its balanced cell-binding affinity triggers fast adsorption-mediated endocytosis. The subsequent Golgi apparatus/endoplasmic reticulum-mediated exocytosis via extracellular vesicles leads to highly effective transcellular delivery and tumor penetration in MTSs. Therefore, the drug carrier's surface cationic charge density critically influences its AMT-induced tumor penetration efficiency. This study provides mechanistic insights into the design of drug-delivery systems with active transcytosis for improved tumor penetration and enhanced therapeutic efficiency.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Biomacromolecules - 22(2021), 12 vom: 13. Dez., Seite 5139-5150 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Siqin [VerfasserIn] |
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| Links: |
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| Themen: |
9002-98-6 |
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| Anmerkungen: |
Date Completed 14.03.2022 Date Revised 14.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.biomac.1c01109 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM333135067 |
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| 520 | |a The adsorption-mediated transcytosis (AMT) induced by the electrostatic interaction between the positively charged surface of carriers and negatively charged cell membrane is a new paradigm enabling nanomedicine's tumor extravasation and infiltration. However, little is known about the correlation between the carrier's charge density and its AMT-induced tumor infiltration efficiency. Herein, we investigate the effect of the cationic polymer's charge on the AMT-induced tumor penetration ability using in vitro multilayer tumor spheroids (MTSs). A cationic polymer, polyethylenimine (PEI), is amidized with acetic anhydride to obtain acetylated PEIs (AcPEIs) with different cationic charge densities. As the amidization ratio increases, the AcPEIs' cytotoxicity, zeta potential, and cell-binding affinity significantly decrease. Notably, not only does the weak cell binding (AcPEIs with high acetylation degrees) lead to slow endocytosis and inefficient transcytosis, so does the strong cell-binding PEI. The PEI with 24% acetylation (AcPEI24%) is found to have the highest transcytosis efficiency because its balanced cell-binding affinity triggers fast adsorption-mediated endocytosis. The subsequent Golgi apparatus/endoplasmic reticulum-mediated exocytosis via extracellular vesicles leads to highly effective transcellular delivery and tumor penetration in MTSs. Therefore, the drug carrier's surface cationic charge density critically influences its AMT-induced tumor penetration efficiency. This study provides mechanistic insights into the design of drug-delivery systems with active transcytosis for improved tumor penetration and enhanced therapeutic efficiency | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Guowei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhuxian |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Jianbin |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Youqing |e verfasserin |4 aut | |
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