Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles
Abstract Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01383-0 |
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| author | Sota Yamada Eita Sasaki Hisashi Ohno Kenjiro Hanaoka |
| author_facet | Sota Yamada Eita Sasaki Hisashi Ohno Kenjiro Hanaoka |
| author_sort | Sota Yamada |
| collection | DOAJ |
| description | Abstract Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively. Upon heating at 42 °C, the micelles aggregated through hydrophobic interaction between their dehydrated shells. Further, the azide moieties of Az-TRM become exposed on the surface due to the thermally shrinkage of the shells, thereby enabling crosslinking between the two types of micelles via azide-alkyne click chemistry to form irreversible aggregates. These aggregates were efficiently accumulated at tumor sites in mice by local heating after intravenous administration of a mixture of the micelles, and were well retained after cessation of heating due to their increased size. As proof of concept, we show that delivery of doxorubicin in this heat-guided drug delivery system dramatically improved the anti-tumor effect in a mouse model after a single treatment. Our results suggest that this platform could be an efficient tool for on-demand drug delivery. |
| format | Article |
| id | doaj-art-5218adde1ed0448399e2ec72be7b1f54 |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-5218adde1ed0448399e2ec72be7b1f542024-12-08T12:21:26ZengNature PortfolioCommunications Chemistry2399-36692024-12-01711910.1038/s42004-024-01383-0Heat-guided drug delivery via thermally induced crosslinking of polymeric micellesSota Yamada0Eita Sasaki1Hisashi Ohno2Kenjiro Hanaoka3Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio UniversityFaculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio UniversityFaculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio UniversityFaculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio UniversityAbstract Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively. Upon heating at 42 °C, the micelles aggregated through hydrophobic interaction between their dehydrated shells. Further, the azide moieties of Az-TRM become exposed on the surface due to the thermally shrinkage of the shells, thereby enabling crosslinking between the two types of micelles via azide-alkyne click chemistry to form irreversible aggregates. These aggregates were efficiently accumulated at tumor sites in mice by local heating after intravenous administration of a mixture of the micelles, and were well retained after cessation of heating due to their increased size. As proof of concept, we show that delivery of doxorubicin in this heat-guided drug delivery system dramatically improved the anti-tumor effect in a mouse model after a single treatment. Our results suggest that this platform could be an efficient tool for on-demand drug delivery.https://doi.org/10.1038/s42004-024-01383-0 |
| spellingShingle | Sota Yamada Eita Sasaki Hisashi Ohno Kenjiro Hanaoka Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles Communications Chemistry |
| title | Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles |
| title_full | Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles |
| title_fullStr | Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles |
| title_full_unstemmed | Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles |
| title_short | Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles |
| title_sort | heat guided drug delivery via thermally induced crosslinking of polymeric micelles |
| url | https://doi.org/10.1038/s42004-024-01383-0 |
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