Construction of Boronophenylalanine-Loaded Biodegradable Periodic Mesoporous Organosilica Nanoparticles for BNCT Cancer Therapy.

Fuyuhiko Tamanoi,Arthur Raitano,Tan Le-Hoang Doan,Aoi Komatsu,Albane Birault,Minoru Suzuki,Shanmugavel Chinnathambi,Ngoc Xuan Dat Mai,Kotaro Matsumoto,Kendall Morrison,Takushi Takata,Mathilde Laird

doi:10.3390/ijms22052251

Fuyuhiko Tamanoi, Arthur Raitano + Show 10 more

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https://doi.org/10.3390/ijms22052251

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Biodegradable periodic mesoporous organosilica (BPMO) has recently emerged as a promising type of mesoporous silica-based nanoparticle for biomedical applications. Like mesoporous silica nanoparticles (MSN), BPMO possesses a large surface area where various compounds can be attached. In this work, we attached boronophenylalanine (10BPA) to the surface and explored the potential of this nanomaterial for delivering boron-10 for use in boron neutron capture therapy (BNCT). This cancer therapy is based on the principle that the exposure of boron-10 to thermal neutron results in the release of α-particles that kill cancer cells. To attach 10BPA, the surface of BPMO was modified with diol groups which facilitated the efficient binding of 10BPA, yielding 10BPA-loaded BPMO (10BPA-BPMO). Surface modification with phosphonate was also carried out to increase the dispersibility of the nanoparticles. To investigate this nanomaterial’s potential for BNCT, we first used human cancer cells and found that 10BPA-BPMO nanoparticles were efficiently taken up into the cancer cells and were localized in perinuclear regions. We then used a chicken egg tumor model, a versatile and convenient tumor model used to characterize nanomaterials. After observing significant tumor accumulation, 10BPA-BPMO injected chicken eggs were evaluated by irradiating with neutron beams. Dramatic inhibition of the tumor growth was observed. These results suggest the potential of 10BPA-BPMO as a novel boron agent for BNCT.

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Biodegradable periodic mesoporous organosilica (BPMO) nanoparticles are a special type of mesoporous silica nanoparticles (MSN) that contain biodegradable chemical bonds such as di- and tetrasulfide bonds within the framework of the nanoparticle [1,2,3,4,5,6]
We set out to explore the use of BPMO to deliver boron-10 that could be used in boron neutron capture therapy (BNCT), a powerful cancer therapy that relies on using neutron exposure of boron-10 [9,10,11,12,13]
The synthesis of BPMO was carried out using bis[3-(triethoxysilyl) propyl] tetrasulfide and 1,2-bis(triethoxysilyl)ethane as precursors of BPMO synthesis, which results in the incorporation of tetrasulfide bonds into the framework of the nanoparticle

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Introduction

Biodegradable periodic mesoporous organosilica (BPMO) nanoparticles are a special type of mesoporous silica nanoparticles (MSN) that contain biodegradable chemical bonds such as di- and tetrasulfide bonds within the framework of the nanoparticle [1,2,3,4,5,6] These nanoparticles have enhanced degradation under reducing conditions such as that encountered inside cells. Like MSN, BPMO nanoparticles have thousands of pores and possess a large surface area to which a variety of compounds can be attached [1,4] They are amenable to various chemical modifications so that surface properties can be altered [1,4]. BNCT is expected to become a widely used cancer therapy in the future

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