Closomers of High Boron Content:  Synthesis, Characterization, and Potential Application as Unimolecular Nanoparticle Delivery Vehicles for Boron Neutron Capture Therapy

Abstract

Unique nanosized closomers of high boron content that may exhibit potential as boron neutron capture therapy target species have been synthesized. The design of these boron-rich nanospheres is based in part on previous work involving dodeca(carboranyl)-substituted closomers [Thomas, J.; Hawthorne, M. F. Chem. Commun. 2001, 1884-1885]. Coupling of ortho-carborane moieties through ester and ether linkages to the rigid [closo-B(12)(OH)(12)](2-) scaffold resulted in the development of a 12(12)-closomer-ester derivative, dodeca[6-(1,2-dicarba-closo-dodecaboran-1-yl)hexanoate]-closo-dodecaborate (2-), 6, and 12(12)-closomer-ether derivatives, dodeca[6-(2-methy1-1,2-dicarba-nido-dodecaboran-1-yl)hexyl]-closo-dodecaborane (14-), 14, and dodeca[6-(7,8-dicarba-nido-dodecaboran-7-yl)hexyl]-closo-dodecaborane (14-), 15. These closomers were investigated by UV-visible spectroscopy and cyclic voltammetry. Additionally, a deboronation method employing NaCN as the nucleophilic reagent was utilized to obtain sodium salts of the ether-linked nido-closomer polyanions, which were purified using a newly developed size-exclusion high pressure liquid chromatography method.

Carboranylporphyrazines for anti-cancer therapies: synthesis and physicochemical properties

“…According to pathway A of Scheme 1, the o-carborane was, in sequence, partially lithiated, protected with TBDMSCl (TBDMSCl = tertbutyl-dimethyl-silyl-cloride) [41, 70,71], treated with n-butyllithium and, finally, in situ, with a large excess of 1,6-dibromohexane to give 3 in a 48% overall yield [17,41]. Spectroscopic characterization data for the intermediates agreed well with available literature data [17,71,72].…”

“…In the past 15 years, several BNCT (Boron Neutron Capture Therapy) agents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] have been proposed, including boronated nucleosides [5][6][7][8][9], amino acids and peptides [10,11], phospholipids [12], monoclonal antibodies, liposomes [13][14][15], closomers [16,17], and dendrimers [18,19]. Tetrapyrrolic macrocycles, a vast class of biologically relevant compounds often employed as sensitizers in anti-cancer photomedical treatments (including photodynamic therapy (PDT) [20][21][22][23][24] and photothermal therapy (PTT) [25][26][27][28]), have also been derivatized with boron-containing functions for possible use in BNCT [20,[29][30][31]…”

The Future of Main Group Chemistry

“…In another interesting study carborane-based nanoparticles with ester or ether linkages have been constructed with the intention that they would mimic liposomes in their ability to pass into the tumor cell vasculature. [147] Although carboranes show great promise as BNCT agents in other medicinal applications, the implementation of these main group drugs will depend on (a) approval for clinical trials by drug administration agencies, and (b) cost considerations. The high cost of synthesizing such specialty drugs is offset, however, by the very low concentrations that are needed for diagnostic applications.…”

Synthesis and Characterization of Carborane Functionalized Dendronized Polymers as Potential Boron Neutron Capture Therapy Agents

“…Therefore, it is theoretically possible to destroy tumor cells without affecting adjacent healthy cells if a sufficiently high 10 B concentration is selectively delivered to the tumor cells. This poses a major challenge to BNCT, as it has been difficult to achieve selective delivery of adequate concentrations of ,0 B, a minimum of 10 9 10 B atoms per cell or approximately 30 jag 10 B per gram of tumor tissue (5,6). One of the most effective ways to address this issue is to incorporate a high number of B atoms within drug delivery vehicles (7).…”

“…To overcome this difficulty, studies have been focused on the development of drug conjugates capable of combining high B content, water solubility and enhanced specific uptake by tumor tissues. Among these studies, conjugation of carborane units with sugars, peptides, DNA (10), antibodies, liposomes (11), and numerous other compounds has received much attention (6,12,13).…”