From monolayer vesicles to micelles (COSAN) or

lamellas (I2-COSAN) in aqueous solution:

New opportunities of boron clusters in medicine Clara Viñas, Francesc Teixidor and Elena Oleshkevich.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., 08193, Bellaterra, Barcelona, Spain.

SELF-ASSEMBLING AND

CELLS’ INTERACTION

Biological interaction with living cells of

COSAN-based synthetic vesicles: These monolayer vesicles have similar dimensions to

biological membranes found in cells, and pass through

synthetic lipid membranes without causing breakdown of

membrane barrier properties. The interaction of these

inorganic membranes system with living cells was also

studied. COSAN has no immediate effect on cell viability,

and cells fully recover when it is removed following

exposure for hours to days. These observations reveal a

new biology at the interface between inorganic, synthetic

COSAN membranes and naturally occurring biological

membranes.

Anionic metallacarboranes display monolayer vesicles of F around 100 nm

and constant wall thickness of 1.16 nm in the mM-mM concentration range of

aqueous solution. Small micelles of approximately 14 molecules of are formed

at higher than 19 mM concentration of COSANE while, 2D lamellas stacked in

(1D smectic order) are formed by mean of intermolecular diH (3.5Å) at higher

concentration of I2-COSAN. COSAN passes through synthetic lipid

membranes without causing breakdown of membrane barrier properties.

References 1 P. Bauduin, S. Prevost, Pau Farràs, F. Teixidor, O. Diat, T. Zemb, Angew.

Chem. Int. Ed. 2011, 50, 5298 –5300.

2 P. Bauduin, D. Brusselle, L. Girard, A. Zaulet, C. Viñas, F. Teixidor, I. Ly, Ol.

Diat, Angew. Chem. Int. Ed. 2013, 52, 12114 –12118.

3 C. Verdiá-Báguena, A. Alcaraz, V. M. Aguilella, A. M. Cioran, S. Tachikawa, H.

Nakamura, F. Teixidor, C. Viñas, Chem. Commun. 2014, 50, 6700-6703.

Monitoring COSAN uptake in living cells by using nB–H Raman spectroscopy.

(A) Comparison of spectral fingerprints of HEK293 cells treated with COSAN 25

mM for 1 hour. (B) Spectra were obtained both inside and outside cells and 4

hours and 4 days after COSAN had been removed, the cells washed and then

replaced in fresh medium. (C) Chemical imaging of HEK293 cell treated with 25

mM COSAN. PC shows phase contrast image while B–H and C–H display

Raman chemical images at 2570 cm-1 (B–H peak) and 2950 cm-1 (C–H peak).

Pink zones in the B–H Raman image show I2-COSAN accumulation inside the

cell, whereas pink zones in the C–H Raman image display high C–H content.

IMAGING

X-ray contrast: A highly radiopaque vertebroplasty bone

cement using tetraiodinated o-carborane

additive was prepared from new radiopaque

microspheres, built from MMA, 4-IEMA, and

a dimethacrylate crosslinker, with I4C2B10H8

embedded therein.

PURELY INORGANIC

NANOPARTICLES (NPs)

Mercaptocarborane-capped gold NPs: 2 nm gold nanoparticles capped with

mercaptocarborane ligands were prepared by a

simple single-phase method. The resultant

monolayer NPs exhibit redox-dependent

solubility and readily phase transfer between

water and nonpolar solvents depending on the

electronic and ionic charge stored in the metal

core and in the ligand shell, respectively.

Carboranyl-capped magnetic NPs aiming towards

multifunctional materials: Purely inorganic superparamagnetic NPs capped with

phosphinic carboranyl clusters were prepared by a

coprecipitation method. Cellular uptake of these NPs

from culture media by two human cell lines related to the

nervous system: capillary-derived human brain

endothelial cells (hCMEC/D3) as well as cancer

glioblastoma multiforme cell line A172 has been proven.

a) Aggregated particles are clearly identified residing within the HeLa cells’

cytoplasm, nucleus and mitochondrion by TEM. b) Confocal microscopy: incubation

with mercaptocarborane-capped NPs causes oxidative stress. ROS monitored by the

appearance of green fluorescence: (a, b) HeLa cells incubated MPCs NPs for 30 min

and (c, d) same as (a) but in the absence of gold NPs. References

1 A. M. Cioran, A. D. Musteti, F. Teixidor, Z. Krpetic, I. A. Prior, Q. He, C. J. Kiely, M. Brust, C. Vinas, J. Am. Chem. Soc. 2012, 134, 212-221.

2 A. M. Cioran, F. Teixidor, Z. Krpetic, M. Brust, C. Vinas, Dalton Trans., 2014, 43, 5054-5061.

ICMAB acknowledges the Severo Ochoa

Program (MINECO, SEV- 2015-0496)

“in vivo” by PET-CT A new bifunctional COSAN derivative incorporating a

PEG arm carrying the “vector” and one iodine atom has

been synthesized and successfully radiolabelled with 124I

(for SPECT biodistribution study) and 125I (for “in vivo”

PET imaging).

ACKNOWLEDGEMENTS

This work was supported by the MINECO grant CTQ2013-44670-R, Generalitat de Catalunya (2014/SGR/149), European Network on Smart Inorganic Polymers (SIPs) (CM1302) and SEA-

on-a-CHIP FP7-OCEAN-2013 (614168).

PC B-H C-H

A

B

1000

1000

3500

2000

3000

1000

1000

0

Ram

an s

igna

l (a.

u.)

1500 2000 2500

4 days after

removal

4 hours after

removal

+ 25 mM cosan

no cosan

2570 cm-1

-1

B-H

C-H

Raman shift (cm )

References 1 M. Tarrés, S. Canetta, C. Viñas, F. Teixidor, A.J. Harwood, Sci. Rep. 2015, 5,

7804-7812.

“in vitro” by Raman Spectroscopy

A) Cellular imaging of HEK293 cells treated with 25 and 2 mM I2-COSAN (in

red; while nucleus in green and membrane in blue). B) A histogram showing the

mean ±SD intensity of the raman B-H peaks for the B-H bond inside and

outside cells (n = 20 cells) after 30 minute incubation; and following wash out in

fresh PBS for 4 hours and 4 days.

HEART

LUNG

LIVER

KIDNEYS

References

1 M. Tarrés, S. Canetta, C. Viñas, F. Teixidor, A. J. Harwood, Chem.

Commun. 2014, 50, 3370-3372.

References

1 A. Pepiol, F. Teixidor, K. Saralidze, C. van der Marel, P.

Willems, L. Voss, M. L.W. Knetsch, C. Vinas, L. H. Koole,

Biomaterials 2011, 32, 6389-6398.

n

References

1 E. Oleshkevich, A. Rosell, A. Morancho, K. Galenkamp,.J. Comella, F.

Teixidor, C. Viñas, under writing.

References

1 K. B. Gona, A. Zaulet, V. Gómez-Vallejo, F. Teixidor, J. Llop, C. Viñas, Chem. Commun.

2014, 50, 11415-11417. ‘Hot Article’.

2 http://blogs.rsc.org/cc/2014/08/19/radiolabels-help-evaluate-emerging-cancer-treatment/