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MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent

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Abstract

Purpose

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser.

Procedures

The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX.

Results

Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm2 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT.

Conclusion

MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

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Acknowledgements

This research was supported by Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and Future Planning (2015R1A2A2A01007798).

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Authors and Affiliations

  1. Department of Radiology, Chonnam National University Hwasun Hospital, Hwasun, 58128, South Korea

    Reju George Thomas, Myeong Ju Moon, Suchithra Poilil Surendran & Yong Yeon Jeong

  2. Biomolecular Theranostics (BiT) Lab, Gwangju, South Korea

    Reju George Thomas, Myeong Ju Moon, Suchithra Poilil Surendran & Yong Yeon Jeong

  3. Medical Photonics Research Center, Korea Photonics Technology Institute, Gwangju, 61007, South Korea

    Hyeong Ju Park & Byeong-Il Lee

  4. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, South Korea

    In-Kyu Park

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  1. Reju George Thomas
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Corresponding author

Correspondence to Yong Yeon Jeong.

Ethics declarations

The animal experiment was conducted in agreement with National Institutes of Health guide for the care and use of Laboratory animals and approved by Chonnam National University Medical School Research Institutional Animal Care and Use Committee (CNUHH 2014-148).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Thomas, R.G., Moon, M.J., Surendran, S.P. et al. MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent. Mol Imaging Biol 20, 533–543 (2018). https://doi.org/10.1007/s11307-018-1169-z

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