Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction <sup>10</sup>B (n, alpha) <sup>7</sup>Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development o...

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Main Authors: Abdul Basith Fithroni, Haruki Inoue, Shengli Zhou, Taufik Fatwa Nur Hakim, Takashi Tada, Minoru Suzuki, Yoshinori Sakurai, Manabu Ishimoto, Naoyuki Yamada, Rani Sauriasari, Wolfgang A. G. Sauerwein, Kazunori Watanabe, Takashi Ohtsuki, Eiji Matsuura
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/1/60
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author Abdul Basith Fithroni
Haruki Inoue
Shengli Zhou
Taufik Fatwa Nur Hakim
Takashi Tada
Minoru Suzuki
Yoshinori Sakurai
Manabu Ishimoto
Naoyuki Yamada
Rani Sauriasari
Wolfgang A. G. Sauerwein
Kazunori Watanabe
Takashi Ohtsuki
Eiji Matsuura
author_facet Abdul Basith Fithroni
Haruki Inoue
Shengli Zhou
Taufik Fatwa Nur Hakim
Takashi Tada
Minoru Suzuki
Yoshinori Sakurai
Manabu Ishimoto
Naoyuki Yamada
Rani Sauriasari
Wolfgang A. G. Sauerwein
Kazunori Watanabe
Takashi Ohtsuki
Eiji Matsuura
author_sort Abdul Basith Fithroni
collection DOAJ
description Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction <sup>10</sup>B (n, alpha) <sup>7</sup>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<sup>®</sup> nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely <i>o</i>-Carborane (Carb) or 1,2-dihexyl-<i>o</i>-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 <sup>10</sup>B-Carb or <sup>10</sup>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 <sup>10</sup>B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with <sup>10</sup>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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institution Kabale University
issn 2073-4409
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publishDate 2025-01-01
publisher MDPI AG
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spelling doaj-art-3ff9323c16b545d081ac576782ca751c2025-01-10T13:16:24ZengMDPI AGCells2073-44092025-01-011416010.3390/cells14010060Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture TherapyAbdul Basith Fithroni0Haruki Inoue1Shengli Zhou2Taufik Fatwa Nur Hakim3Takashi Tada4Minoru Suzuki5Yoshinori Sakurai6Manabu Ishimoto7Naoyuki Yamada8Rani Sauriasari9Wolfgang A. G. Sauerwein10Kazunori Watanabe11Takashi Ohtsuki12Eiji Matsuura13Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, JapanJ-BEAM, Inc., Fukushima 979-0513, JapanNihon Fukushi Fuiin Holding, Co., Ltd., Fukushima 979-0513, JapanFaculty of Pharmacy, Universitas Indonesia, Depok 16424, IndonesiaDeutsche Gesellschaft für Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik für Strahlentherapie, 45122 Essen, GermanyGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanBoron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction <sup>10</sup>B (n, alpha) <sup>7</sup>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<sup>®</sup> nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely <i>o</i>-Carborane (Carb) or 1,2-dihexyl-<i>o</i>-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 <sup>10</sup>B-Carb or <sup>10</sup>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 <sup>10</sup>B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with <sup>10</sup>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”.https://www.mdpi.com/2073-4409/14/1/60boron neutron capture therapy (BNCT)dual therapeutic effectsLactosome<sup>®</sup>hydrophobic boron compoundneutron irradiationtheranostics
spellingShingle Abdul Basith Fithroni
Haruki Inoue
Shengli Zhou
Taufik Fatwa Nur Hakim
Takashi Tada
Minoru Suzuki
Yoshinori Sakurai
Manabu Ishimoto
Naoyuki Yamada
Rani Sauriasari
Wolfgang A. G. Sauerwein
Kazunori Watanabe
Takashi Ohtsuki
Eiji Matsuura
Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
Cells
boron neutron capture therapy (BNCT)
dual therapeutic effects
Lactosome<sup>®</sup>
hydrophobic boron compound
neutron irradiation
theranostics
title Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
title_full Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
title_fullStr Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
title_full_unstemmed Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
title_short Novel Drug Delivery Particles Can Provide Dual Effects on Cancer “Theranostics” in Boron Neutron Capture Therapy
title_sort novel drug delivery particles can provide dual effects on cancer theranostics in boron neutron capture therapy
topic boron neutron capture therapy (BNCT)
dual therapeutic effects
Lactosome<sup>®</sup>
hydrophobic boron compound
neutron irradiation
theranostics
url https://www.mdpi.com/2073-4409/14/1/60
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