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Theranostics 2019; 9(2):381-390. doi:10.7150/thno.28376 This issue Cite

Research Paper

Highly-Soluble Cyanine J-aggregates Entrapped by Liposomes for In Vivo Optical Imaging around 930 nm

Dyego Miranda^1*, Haoyuan Huang^1*, Homan Kang², Ye Zhan¹, Depeng Wang¹, Yang Zhou³, Jumin Geng¹, Hailey I. Kilian¹, Wesley Stiles², Aida Razi⁴, Joaquin Ortega⁴, Jun Xia¹, Hak Soo Choi², Jonathan F. Lovell^1✉

1. Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
2. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
3. College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
4. Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 0C7, Canada
*Equal contribution

✉ Corresponding author: jflovelledu

Abstract

Near infrared (NIR) dyes are useful for in vivo optical imaging. Liposomes have been used extensively for delivery of diverse cargos, including hydrophilic cargos which are passively loaded in the aqueous core. However, most currently available NIR dyes are only slightly soluble in water, making passive entrapment in liposomes challenging for achieving high optical contrast.

Methods: We modified a commercially-available NIR dye (IR-820) via one-step Suzuki coupling with dicarboxyphenylboronic acid, generating a disulfonated heptamethine; dicarboxyphenyl cyanine (DCP-Cy). DCP-Cy was loaded in liposomes and used for optical imaging.

Results: Owing to increased charge in mildly basic aqueous solution, DCP-Cy had substantially higher water solubility than indocyanine green (by an order of magnitude), resulting in higher NIR absorption. Unexpectedly, DCP-Cy tended to form J-aggregates with pronounced spectral red-shifting to 934 nm (from 789 nm in monomeric form). J-aggregate formation was dependent on salt and DCP-Cy concentration. Dissolved at 20 mg/mL, DCP-Cy J-aggregates could be entrapped in liposomes. Full width at half maximum absorption of the liposome-entrapped dye was just 25 nm. The entrapped DCP-Cy was readily detectable by fluorescence and photoacoustic NIR imaging. Upon intravenous administration to mice, liposomal DCP-Cy circulated substantially longer than the free dye. Accumulation was largely in the spleen, which was visualized with fluorescence and photoacoustic imaging.

Conclusions: DCP-Cy is simple to synthesize and exhibits high aqueous solubility and red-shifted absorption from J-aggregate formation. Liposomal dye entrapment is possible, which facilitates in vivo photoacoustic and fluorescence imaging around 930 nm.

Keywords: cyanine, J-aggregate, liposomes, photoacoustic

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