In Vitro and In Vivo Evaluation of Fluorescently Labeled Borocaptate-Containing Liposomes.

Abstract

Boron neutron capture therapy (BNCT), a binary cancer therapeutic modality, has moved to a new phase since development of accelerator-based neutron sources and establishment of BNCT centers in Finland and Japan. That stimulated efforts for better boron delivery agent development. As liposomes have shown effective boron delivery properties and sufficient tumor retention, fluorescent liposome labelling may serve as a rapid method to study initial ability of newly synthesized liposomes to be captured by tumor cells prior to experiments on boron accumulation and neutron irradiation. In this work, we studied the accumulation and biodistribution of pegylated liposomes with encapsulated borocaptate (BSH) and a fluorescent label (Nile Red) in U87 (human glioblastoma), SW-620 (human colon carcinoma), SK-MEL-28 (human melanoma), FetMSC (mesenchymal human embryo stem cells), and EMBR (primary embryocytes) cell lines as well as an orthotopic xenograft model of U87 glioma in SCID mice. Results indicate that fluorescent microscopy is effective at determining the intracellular localization of the liposomes using a fluorescent label. The synthesized, pegylated liposomes showed higher accumulation in tumors compared to normal cells, with characteristic concentration peaks in SW-620 and U87 cell lines, and provided in vivo tumor selectivity with several-fold higher tumor tissue fluorescence at the 6-h timepoint. Graphical abstract Fluorescent images of U-87 glioma cells after 24 hours of incubation with BSH-containing liposomes labeled with lipophilic Nile Red (red color)and water-soluble FITC-Dextran (green color); cell nuclei in blue color (DAPI-staining) (×400). Scale bar is 50 μm. Fluorescent labelling serves as anexpress method to study liposome delivery efficiency prior to boron accumulation evaluation and BNCT irradiation experiments.

• Authors: Vladimir Kanygin, Alexander Zaboronok, Iuliia Taskaeva, Evgenii Zavjalov, Rinat Mukhamadiyarov, Aleksandr Kichigin, Anna Kasatova, Ivan Razumov, Roman Sibirtsev, Bryan J Mathis
• Journal: Journal of fluorescence (J Fluoresc) Vol. 31 Issue 1 Pg. 73-83 (Jan 2021) ISSN: 1573-4994 [Electronic] Netherlands
• PMID: 33078252 (Publication Type: Journal Article)

Chemical References

• Borohydrides
• Fluorescent Dyes
• Liposomes

Topics

• Borohydrides (chemistry, therapeutic use)
• Cell Line, Tumor
• Fluorescent Dyes (chemistry)
• Glioma (pathology)
• Humans
• Liposomes (chemistry)