Hyaluronate siRNA nanoparticles with positive charge display rapid attachment to tumor endothelium and penetration into tumors
Copyright © 2020 Elsevier B.V. All rights reserved..
A cationizable sequence-defined lipo-oligoaminoamide (lipo-OAA) conferring stable assembly of siRNA into ~200 nm sized complexes contains an N-terminal azidolysine for covalent coating of formed nanoparticles with dibenzocyclooctyne-amine (DBCO)-modified hyaluronic acid (HA). Depending on the applied equivalents of DBCO-HA, stable nanoparticles with either cationic or anionic surface charge can be formed. The unmodified and two types of covalent HA-modified siRNA nanoparticles differ in their biological characteristics. Both types of HA coated siRNA complexes show an enhanced cellular uptake over uncoated complexes and facilitate efficient gene silencing, but differ in intracellular uptake pathways and distribution. Upon intravenous administration in mice, beyond our expectation and in contrast to the in vitro findings, only the cationic HA nanoparticles but neither the non-coated cationic nor the anionic HA complexes were able to target subcutaneous Huh 7 tumors and exert potent (78%) gene silencing. The favorable and very fast accumulation of cationic HA nanoparticles was confirmed in another subcutaneous tumor model. As evidenced by 3D nanoparticle distribution within Huh 7 tumors evaluated at early time points of 5 min and 45 min, only the cationic HA-based nanoparticles rapidly attach to the tumor endothelium and subsequently penetrate into tumor, in contrast to the analogous anionic HA coated or the cationic non-coated formulation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:329 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 329(2021) vom: 10. Jan., Seite 919-933 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Luo, Jie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.07.2021 Date Revised 07.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2020.10.022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316391743 |
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| 245 | 1 | 0 | |a Hyaluronate siRNA nanoparticles with positive charge display rapid attachment to tumor endothelium and penetration into tumors |
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| 500 | |a Date Revised 07.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a A cationizable sequence-defined lipo-oligoaminoamide (lipo-OAA) conferring stable assembly of siRNA into ~200 nm sized complexes contains an N-terminal azidolysine for covalent coating of formed nanoparticles with dibenzocyclooctyne-amine (DBCO)-modified hyaluronic acid (HA). Depending on the applied equivalents of DBCO-HA, stable nanoparticles with either cationic or anionic surface charge can be formed. The unmodified and two types of covalent HA-modified siRNA nanoparticles differ in their biological characteristics. Both types of HA coated siRNA complexes show an enhanced cellular uptake over uncoated complexes and facilitate efficient gene silencing, but differ in intracellular uptake pathways and distribution. Upon intravenous administration in mice, beyond our expectation and in contrast to the in vitro findings, only the cationic HA nanoparticles but neither the non-coated cationic nor the anionic HA complexes were able to target subcutaneous Huh 7 tumors and exert potent (78%) gene silencing. The favorable and very fast accumulation of cationic HA nanoparticles was confirmed in another subcutaneous tumor model. As evidenced by 3D nanoparticle distribution within Huh 7 tumors evaluated at early time points of 5 min and 45 min, only the cationic HA-based nanoparticles rapidly attach to the tumor endothelium and subsequently penetrate into tumor, in contrast to the analogous anionic HA coated or the cationic non-coated formulation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cationic and anionic nanoparticles | |
| 650 | 4 | |a Click chemistry | |
| 650 | 4 | |a Gene silencing | |
| 650 | 4 | |a Hyaluronic acid | |
| 650 | 4 | |a Lipo-oligomer | |
| 650 | 4 | |a Penetration | |
| 650 | 4 | |a siRNA | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Hyaluronic Acid |2 NLM | |
| 650 | 7 | |a 9004-61-9 |2 NLM | |
| 700 | 1 | |a Schmaus, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Mochen |e verfasserin |4 aut | |
| 700 | 1 | |a Hörterer, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wilk, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Höhn, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Däther, Maike |e verfasserin |4 aut | |
| 700 | 1 | |a Berger, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Benli-Hoppe, Teoman |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Lun |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Ernst |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jconrel.2020.10.022 |3 Volltext |
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