Self-assembled Nanogels of Carborane-bearing Polysaccharides for Boron Neutron Capture Therapy

Abstract

Carborane shows high levels of hydrophobicity, thermal stability, and chemical stability. The hydrophobicity of carborane has been used to form interactions with the hydrophobic core of bioactive proteins. We have designed and synthesized carborane-bearing pullulan using carborane as a hydrophobic core to prepare physically crosslinked nanogels. The resulting amphiphilic polysaccharide formed stable self-assembled nanogels through a complex network of hydrophobic interactions. Carborane can be used to achieve efficient boron neutron capture therapy (BNCT) 1 because every molecule of this material is capable of delivering a high dose of boron. BNCT is a cellselective radiation technique that can be used to treat cancer.2 In terms of its therapeutic application, BNCT involves the use of α-particles and lithium nuclei, which are generated by the release of low-energy thermal neutron irradiation from boron via the boron neutron capture reaction. The energy emitted from the nuclei can lead to cell destruction, bouncing out up to 10¯m.1 The bouncing range of this technique corresponds to the size of a single cell, suggesting that BNCT could be used to selectively kill specific cells at the irradiated site without injuring normal tissues, if boron could be selectively delivered to tumor cells. In light of its therapeutic potential for the treatment of cancer, BNCT has been applied to a variety of malignant tumors, including melanoma 3 and glioblastoma, 4 where invasive techniques are generally poorly tolerated. The success of BNCT is dependent on the effectiveness with which highly concentrated 10 B particles can be delivered to cancer cells. 5 The development of effective boron carrier systems capable of increasing the therapeutic value on BNCT are therefore highly desired. 68 Herein, we reported the development of carborane-bearing polysaccharides, which undergo an efficient self-assembly process in water to form highly integrated boron clusters (Figure 1). Carborane shows high levels of hydrophobicity, thermal stability, and chemical stability. 912 The partial grafting of hydrophilic pullulan with carborane resulted in the formation of self-assembled nanogels through a series of hydrophobic interactions between the carboranes. It is envisaged that the integrated boron clusters formed in this way will show higher neutron capture efficiency than conventional polymer-based boron agents.Amphiphilic polysaccharides such as cholesterol-bearing pullulan (CHP) form stable physically crosslinked nanogels in water through hydrophobic interactions.1316 Self-assembly strategies can be used to form various functional nanogels. As shown in Figure 2, carborane-bearing pullulans (CAPs) were

Water Solubilization and Thermal Stimuli-Triggered Release of Porphyrin Derivatives Using Thermoresponsive Polysaccharide Hydroxypropyl Cellulose for Mitochondria-Targeted Photodynamic Therapy

“…We attribute these thermoresponsive changes in the photochemical properties of THPP-HPC complexes to the changes in the hydrophobicity of the polymer matrix in HPC through pyrene. The ratio of the fluorescence intensities of pyrene at the emission wavelengths of 375 ( I 375 ) and 385 nm ( I 385 ) ( I 375 / I 385 ) is known as an indicator of the polarity of a microenvironment . Dissociated pyrene in a polar medium such as water results in an I 375 / I 385 value of 1.75.…”

“…The ratio of the fluorescence intensities of pyrene at the emission wavelengths of 375 (I 375 ) and 385 nm (I 385 ) (I 375 /I 385 ) is known as an indicator of the polarity of a microenvironment. 30 Dissociated pyrene in a polar medium such as water results in an I 375 /I 385 value of 1.75. In contrast, the I 375 /I 385 ratio of HPC at 25 and 55 °C were 1.2 and 1.15, respectively (Figure S8).…”

Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors

“…When boron delivery agents enter tumor tissues and enrich tumor cells, the thermal neutrons trigger fission of boron atoms, which leads to release of 10 B atoms and then release of α particles ( 4 He) and recoil lithium particles ( 7 Li) [104,105]. The released α particles are toxic for cells and can result in cell destruction, bouncing out up to 10 µm, which is almost the size of the cells; for this reason this technique is called cell-selective radiation therapy [106]. The first clinical use of sodium borocaptate (BSH) for BNCT was reported by the Japanese scientist Hiroshi Hatanaka in 1960; boronophenylalanine (BPA) was introduced for clinical use by another Japanese scientist Y. Mishima in 1988-1989 [107].…”

Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy

“…Boron-based nanomaterials [18][19][20][21], such as polymers [22], liposomes [23][24][25][26], boron nitride [20,27] and other types of nanoparticles, were also developed [28][29][30][31][32][33].…”