Effects of Linkers on the Development of Liposomal Formulation of Cholesterol Conjugated Cobalt Bis(dicarbollides)

Synthesis and Structure of Nido-Carboranyl Azide and Its “Click” Reactions

“…Recently, using "click" reactions we obtained a series of mono-negative charged conjugates of cobalt bis(dicarbollide) with cholesterol [47], conjugates of cobalt/iron of bis(dicarbollide) and cholesterol with similar length spacer but with zwitter-ionic character of target molecule [48] and conjugates of closo-dodecaborate dianion with cholesterol [49]. It has been only recently shown that the inclusion of lipophilic boron-containing species in the liposome bilayer provides an attractive method to increase the gross boron content of the liposomes in the formulation [50,51]. In addition, it has been found that PEGylated liposome encapsulating nido-carborane by hydrating thin lipid films significantly suppresses tumors in boron neutron capture therapy [52].…”

Synthesis of Zwitter-Ionic Conjugate of Nido-Carborane with Cholesterol

“…Among the methods for obtaining bioconjugates, the Cu(I)-catalyzed 1,3-dipolar [3+2] cycloaddition reaction of alkynes to azides is widely used, leading to the formation of 1,2,3 triazoles; this is known as the "click"-reaction" [34][35][36]. Earlier, the "click"-reaction was successfully used to obtain a wide range of conjugates of polyhedral boron hydrides with various biologically active molecules, such as nucleosides [37] and chlorine e 6 [38], as well as derivatives of cholesterol based on cobalt/iron bis(dicarbollide) [26,27,33,39], closo-dodecaborate dianion [40] and nido-carborane [41]. In this work, we used cholesterol derivatives, as well as 3β-(2-azido-ethoxy)cholest-5-ene and nido-carboranyl derivatives, that contained different spacers between the boron cage and the terminal acetylene group.…”

“…The product was purified on a silica column using CH 2 Cl 2 -CH 3 CN (7:1) as an eluent to give the white solid of 6 (0.10 g, yield 72%). 1 (26)H 3 ), 0.88 (3H, s, C st (27)H 3 ), 0.73 (3H, s, C st (18)…”

“…Therefore, the design of stable biocompatible boron-containing cholesterol nanostructures for the further creation of liposomal agents that contain derivatives of polyhedral boron hydrides is an effective approach that can solve the problem of the selective delivery of boron into tumor cells required to carry out BNCT. It was also recently shown that the inclusion of lipophilic boron-containing species in the bilayer of liposomes provides an attractive means of increasing the total boron content in liposomes contained within the formulation [26,27]. In addition, it was found that the encapsulation of nido-carborane with PEGylated liposome via the hydration of thin lipid films significantly suppresses tumors in BNCT [28].…”

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide)

“…Cobalt bis(dicarbollide) [3,3 -Co(1,2-C 2 B 9 H 11 ) 2 ] − is the most available and the most stable of metallacarboranes [1][2][3][4], which attracts considerable attention of researchers due to possibility of its use in a variety of fields, from the development of new materials [5][6][7][8][9][10][11][12] to medicine [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Therefore, the development of new convenient methods for the functionalization of cobalt bis(dicarbollide) cobalt is an important task [3,4].…”