Fithroni Abdul Basith, Inoue Haruki, Zhou Shengli, Hakim Taufik Fatwa Nur, Tada Takashi, Suzuki Minoru, Sakurai Yoshinori, Ishimoto Manabu, Yamada Naoyuki, Sauriasari Rani, Sauerwein Wolfgang A G, Watanabe Kazunori, Ohtsuki Takashi, Matsuura Eiji
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan.
Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
Cells. 2025 Jan 6;14(1):60. doi: 10.3390/cells14010060.
Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction B (n, alpha) Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, "AB-type" Lactosome nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely -Carborane (Carb) or 1,2-dihexyl--Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the "molecular glue" effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either B-Carb or B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., "theranostics".
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