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- Publisher Website: 10.1021/bm101517x
- Scopus: eid_2-s2.0-79953854925
- PMID: 21344942
- WOS: WOS:000289223500042
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Article: Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin
Title | Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin |
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Authors | |
Issue Date | 2011 |
Citation | Biomacromolecules, 2011, v. 12, n. 4, p. 1224-1233 How to Cite? |
Abstract | A biocompatible, robust polymer micelle bearing pH-hydrolyzable shell cross-links was developed for efficient intracellular delivery of doxorubicin (DOX). The rationally designed triblock copolymer of poly(ethylene glycol)-poly(l-aspartic acid)-poly(l-phenylalanine) (PEG-PAsp-PPhe) self-assembled to form polymer micelles with three distinct domains of the PEG outer corona, the PAsp middle shell, and the PPhe inner core. Shell cross-linking was performed by the reaction of ketal-containing cross-linkers with Asp moieties in the middle shells. The shell cross-linking did not change the micelle size and the spherical morphology. Fluorescence quenching experiments confirmed the formation of shell cross-linked diffusion barrier, as judged by the reduced SterñVolmer quenching constant (KSV). Dynamic light scattering and fluorescence spectroscopy experiments showed that shell cross-linking improved the micellar physical stability even in the presence of micelle disrupting surfactants, sodium dodecyl sulfate (SDS). The hydrolysis kinetics study showed that the hydrolysis half-life (t1/2) of ketal cross-links was estimated to be 52 h at pH 7.4, whereas 0.7 h at pH 5.0, indicating the 74-fold faster hydrolysis at endosomal pH. Ketal cross-linked micelles showed the rapid DOX release at endosomal pH, compared to physiological pH. Confocal laser scanning microscopy (CLSM) showed that ketal cross-linked micelles were taken up by the MCF-7 breast cancer cells via endocytosis and transferred into endosomes to hydrolyze the cross-links by lowered pH and finally facilitate the DOX release to inhibit proliferation of cancer cells. This ketal cross-linked polymer micelle is promising for enhanced intracellular delivery efficiency of many hydrophobic anticancer drugs. © 2011 American Chemical Society. |
Persistent Identifier | http://hdl.handle.net/10722/323853 |
ISSN | 2023 Impact Factor: 5.5 2023 SCImago Journal Rankings: 1.232 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lee, Sang Jin | - |
dc.contributor.author | Min, Kyung Hyun | - |
dc.contributor.author | Lee, Hong Jae | - |
dc.contributor.author | Koo, Ahn Na | - |
dc.contributor.author | Rim, Hwa Pyeong | - |
dc.contributor.author | Jeon, Byeong Jin | - |
dc.contributor.author | Jeong, Seo Young | - |
dc.contributor.author | Heo, Jung Sun | - |
dc.contributor.author | Lee, Sang Cheon | - |
dc.date.accessioned | 2023-01-13T02:59:46Z | - |
dc.date.available | 2023-01-13T02:59:46Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Biomacromolecules, 2011, v. 12, n. 4, p. 1224-1233 | - |
dc.identifier.issn | 1525-7797 | - |
dc.identifier.uri | http://hdl.handle.net/10722/323853 | - |
dc.description.abstract | A biocompatible, robust polymer micelle bearing pH-hydrolyzable shell cross-links was developed for efficient intracellular delivery of doxorubicin (DOX). The rationally designed triblock copolymer of poly(ethylene glycol)-poly(l-aspartic acid)-poly(l-phenylalanine) (PEG-PAsp-PPhe) self-assembled to form polymer micelles with three distinct domains of the PEG outer corona, the PAsp middle shell, and the PPhe inner core. Shell cross-linking was performed by the reaction of ketal-containing cross-linkers with Asp moieties in the middle shells. The shell cross-linking did not change the micelle size and the spherical morphology. Fluorescence quenching experiments confirmed the formation of shell cross-linked diffusion barrier, as judged by the reduced SterñVolmer quenching constant (KSV). Dynamic light scattering and fluorescence spectroscopy experiments showed that shell cross-linking improved the micellar physical stability even in the presence of micelle disrupting surfactants, sodium dodecyl sulfate (SDS). The hydrolysis kinetics study showed that the hydrolysis half-life (t1/2) of ketal cross-links was estimated to be 52 h at pH 7.4, whereas 0.7 h at pH 5.0, indicating the 74-fold faster hydrolysis at endosomal pH. Ketal cross-linked micelles showed the rapid DOX release at endosomal pH, compared to physiological pH. Confocal laser scanning microscopy (CLSM) showed that ketal cross-linked micelles were taken up by the MCF-7 breast cancer cells via endocytosis and transferred into endosomes to hydrolyze the cross-links by lowered pH and finally facilitate the DOX release to inhibit proliferation of cancer cells. This ketal cross-linked polymer micelle is promising for enhanced intracellular delivery efficiency of many hydrophobic anticancer drugs. © 2011 American Chemical Society. | - |
dc.language | eng | - |
dc.relation.ispartof | Biomacromolecules | - |
dc.title | Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1021/bm101517x | - |
dc.identifier.pmid | 21344942 | - |
dc.identifier.scopus | eid_2-s2.0-79953854925 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1224 | - |
dc.identifier.epage | 1233 | - |
dc.identifier.eissn | 1526-4602 | - |
dc.identifier.isi | WOS:000289223500042 | - |