An Amphiphilic Cell‐Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9
Abstract: The discovery of safe platforms that can circumvent the endocytic pathway is of great significance for biological therapeutics that are usually degraded during endocytosis. Here we show that a self‐assembled and dynamic macrocycle can passively diffuse through the cell membrane and deliver a broad range of biologics, including proteins, CRISPR Cas9, and ssDNA, directly to the cytosol while retaining their bioactivity. Cell‐penetrating macrocycle CPM can be easily prepared from the room temperature condensation of diketopyrrolopyrrole lactams with diamines. We attribute the high cellular permeability of CPM to its amphiphilic nature and chameleonic properties. It adopts conformations that partially bury polar groups and expose hydrophobic side chains, thus self‐assembling into micellar‐like structures. Its superior fluorescence makes CPM trackable inside cells where it follows the endomembrane system. CPM outperformed commercial reagents for biologics delivery and showed high RNA knockdown efficiency of CRISPR Cas9. We envisage that this macrocycle will be an ideal starting point to design and synthesize biomimetic macrocyclic tags that can readily facilitate the interaction and uptake of biomolecules and overcome endosomal digestion.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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An Amphiphilic Cell‐Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9 ; day:30 ; month:06 ; year:2024 ; extent:9
Angewandte Chemie / International edition. International edition ; (30.06.2024) (gesamt 9)
- Creator
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Qutub, Somayah S.
Bhat, Imtiyaz Ahmad
Maatouk, Batoul I.
Moosa, Basem
Fakim, Aliyah
Nawaz, Kashif
Diaz‐Galicia, Escarlet
Lin, Weibin
Grünberg, Raik
Arold, Stefan T.
Khashab, Niveen M.
- DOI
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10.1002/anie.202403647
- URN
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urn:nbn:de:101:1-2407011408533.298421872832
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:51 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Qutub, Somayah S.
- Bhat, Imtiyaz Ahmad
- Maatouk, Batoul I.
- Moosa, Basem
- Fakim, Aliyah
- Nawaz, Kashif
- Diaz‐Galicia, Escarlet
- Lin, Weibin
- Grünberg, Raik
- Arold, Stefan T.
- Khashab, Niveen M.
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An Amphiphilic Cell‐Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9
A Quantitative Method to Distinguish Cytosolic from Endosome‐Trapped Cell‐Penetrating Peptides
Cellular Uptake of Cell‐Penetrating Peptides Activated by Amphiphilic p‐Sulfonatocalix (4) arenes
Small Macrocycle Rotaxanes in High Yields
Modern supramolecular chemistry : strategies for macrocycle synthesis
Multimodal switching of a redox-active macrocycle
The macrocycle inhibitor landscape of SLC‐transporter
Two macrocycle-based sensors for anions sensing
A Bis‐Perylene Diimide Macrocycle Chiroptical Switch
A Bis‐Perylene Diimide Macrocycle Chiroptical Switch
Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle
Display Selection of a Hybrid Foldamer–Peptide Macrocycle
An Amphiphilic Cell‐Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9
A Quantitative Method to Distinguish Cytosolic from Endosome‐Trapped Cell‐Penetrating Peptides
Cellular Uptake of Cell‐Penetrating Peptides Activated by Amphiphilic p‐Sulfonatocalix (4) arenes
Small Macrocycle Rotaxanes in High Yields
Modern supramolecular chemistry : strategies for macrocycle synthesis
Multimodal switching of a redox-active macrocycle
The macrocycle inhibitor landscape of SLC‐transporter
Two macrocycle-based sensors for anions sensing
A Bis‐Perylene Diimide Macrocycle Chiroptical Switch
A Bis‐Perylene Diimide Macrocycle Chiroptical Switch
Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle