A mRNA-Responsive G-Quadruplex-Based Drug Release System
1
Advanced Research Division, Panasonic Corporation, 3-4 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan
2
Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
3
Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Matteo Castronovo
Sensors 2015, 15(4), 9388-9403; https://doi.org/10.3390/s150409388
Received: 6 February 2015
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Revised: 8 April 2015
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Accepted: 8 April 2015
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Published: 21 April 2015
(This article belongs to the Special Issue Next-Generation Nucleic Acid Sensors)
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.
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Keywords:
drug delivery carrier; G-quadruplex; anionic phthalocyanine; cancer; mRNA; telomerase
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MDPI and ACS Style
Yaku, H.; Murashima, T.; Miyoshi, D.; Sugimoto, N. A mRNA-Responsive G-Quadruplex-Based Drug Release System. Sensors 2015, 15, 9388-9403. https://doi.org/10.3390/s150409388
AMA Style
Yaku H, Murashima T, Miyoshi D, Sugimoto N. A mRNA-Responsive G-Quadruplex-Based Drug Release System. Sensors. 2015; 15(4):9388-9403. https://doi.org/10.3390/s150409388
Chicago/Turabian StyleYaku, Hidenobu, Takashi Murashima, Daisuke Miyoshi, and Naoki Sugimoto. 2015. "A mRNA-Responsive G-Quadruplex-Based Drug Release System" Sensors 15, no. 4: 9388-9403. https://doi.org/10.3390/s150409388
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