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Nano Research 2018, 11(2): 1082-1098 https://doi.org/10.1007/s12274-017-1728-7
Research Article | Issue | Published: 29 August 2017

Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery

Show Author's Information Ka Young Kim1,§,  Hanyong Jin2,§,  Jaehyeon Park1,  Sung Ho Jung1,  Ji Ha Lee1,  Hyesong Park1,  Sung Kuk Kim1,  Jeehyeon Bae2,  Jong Hwa Jung1( )
Department of Chemistry and Research Institute of Natural SciencesGyeongsang National UniversityJinju52828Republic of Korea
School of PharmacyChung-Ang UniversitySeoul06974Republic of Korea

§Ka Young Kim and Hanyong Jin contributed equally to this work.

Keywords:
fluorescence imaging, drug delivery, aggregation-induced emission, mitochondria-targeting, chemotherapy
An erratum to this article is available online at https://doi.org/10.1007/s12274-017-1846-2
Cite this article:
Kim KY, Jin H, Park J, et al. Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery. Nano Research, 2018, 11(2): 1082-1098. https://doi.org/10.1007/s12274-017-1728-7
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Abstract Full text Electronic supplementary material About this article

Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission (AIE). The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanoparticles with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles (N1) selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin (DOX), to the mitochondria with high efficiency. More importantly, N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intracellular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and N1-encapsulated doxorubicin (N1-DOX) effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.


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About this article

Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery

Show Author's information Ka Young Kim1,§, Hanyong Jin2,§, Jaehyeon Park1, Sung Ho Jung1, Ji Ha Lee1, Hyesong Park1, Sung Kuk Kim1, Jeehyeon Bae2, Jong Hwa Jung1( )
Department of Chemistry and Research Institute of Natural SciencesGyeongsang National UniversityJinju52828Republic of Korea
School of PharmacyChung-Ang UniversitySeoul06974Republic of Korea

§Ka Young Kim and Hanyong Jin contributed equally to this work.

Abstract

Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission (AIE). The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanoparticles with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles (N1) selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin (DOX), to the mitochondria with high efficiency. More importantly, N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intracellular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and N1-encapsulated doxorubicin (N1-DOX) effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.

Keywords: fluorescence imaging, drug delivery, aggregation-induced emission, mitochondria-targeting, chemotherapy

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Publication history
Copyright
Acknowledgements

Publication history

Received: 01 April 2017
Revised: 13 June 2017
Accepted: 22 June 2017
Published: 29 August 2017
Issue date: February 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany 2017

Acknowledgements

Acknowledgements

This work was supported by a grant from NRF (Nos. 2017R1A4A1014595 and 2015R1A2A2A05001400). In addition, this work was partially supported by a grant from the Next-Generation BioGreen 21 Program (SSAC, No. PJ011177022016), Rural development Administration, Korea.

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