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

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Nano Research 2018年第2期11卷 1082-1098页

作者： Ka Young Kim Hanyong Jin Jaehyeon park Sung Ho Jung Ji Ha Lee hyesong park Sung Kuk Kim Jeehyeon Bae Jong Hwa Jung Department of Chemistry and Research Institute of Natural Sciences Gyeongsang National University Jinju Republic of Korea School of Pharmacy Chung-Ang University Seoul Republic of Korea

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 nanopartides 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 importantl~ 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 intraceUular 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 Nl-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.

关键词： aggregation-inducedemission,chemotherap3 drug deliver3 mitochondria-targeting,fluorescence imaging

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