A mRNA-Responsive G-Quadruplex-Based Drug Release System
G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-04-01
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| Series: | Sensors |
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| Online Access: | http://www.mdpi.com/1424-8220/15/4/9388 |
| _version_ | 1828153829131026432 |
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| author | Hidenobu Yaku Takashi Murashima Daisuke Miyoshi Naoki Sugimoto |
| author_facet | Hidenobu Yaku Takashi Murashima Daisuke Miyoshi Naoki Sugimoto |
| author_sort | Hidenobu Yaku |
| collection | DOAJ |
| description | G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA. |
| first_indexed | 2024-04-11T22:30:46Z |
| format | Article |
| id | doaj.art-03dc2d20de0740a1bbeaa2ccf060303e |
| institution | Directory Open Access Journal |
| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-04-11T22:30:46Z |
| publishDate | 2015-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Sensors |
| spelling | doaj.art-03dc2d20de0740a1bbeaa2ccf060303e2022-12-22T03:59:24ZengMDPI AGSensors1424-82202015-04-011549388940310.3390/s150409388s150409388A mRNA-Responsive G-Quadruplex-Based Drug Release SystemHidenobu Yaku0Takashi Murashima1Daisuke Miyoshi2Naoki Sugimoto3Advanced Research Division, Panasonic Corporation, 3-4 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0237, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanG-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA.http://www.mdpi.com/1424-8220/15/4/9388drug delivery carrierG-quadruplexanionic phthalocyaninecancermRNAtelomerase |
| spellingShingle | Hidenobu Yaku Takashi Murashima Daisuke Miyoshi Naoki Sugimoto A mRNA-Responsive G-Quadruplex-Based Drug Release System Sensors drug delivery carrier G-quadruplex anionic phthalocyanine cancer mRNA telomerase |
| title | A mRNA-Responsive G-Quadruplex-Based Drug Release System |
| title_full | A mRNA-Responsive G-Quadruplex-Based Drug Release System |
| title_fullStr | A mRNA-Responsive G-Quadruplex-Based Drug Release System |
| title_full_unstemmed | A mRNA-Responsive G-Quadruplex-Based Drug Release System |
| title_short | A mRNA-Responsive G-Quadruplex-Based Drug Release System |
| title_sort | mrna responsive g quadruplex based drug release system |
| topic | drug delivery carrier G-quadruplex anionic phthalocyanine cancer mRNA telomerase |
| url | http://www.mdpi.com/1424-8220/15/4/9388 |
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