ISMSC 2007 - Università degli Studi di Pavia

PSA 9
Cell penetrating borosilica nanoparticles: potential delivery agents for BNCT
Maria Arduini 1 , Giuliana Battanolli 1 , Luca Baù 1 , Fabrizio Mancin 1 , Umberto Tonellato 1 , Chiara
Compagnin 2 , Lucia Celotti 2 , Maddalena Mognato 2 , Elena Reddi 2
1 University of Padova, Department of Chemical Sciences, via Marzolo 1, 35131, Padova, Italy
2 University of Padova, Department of Biology, via Bassi 58/B, 35121, Padova, Italy
Boron neutron capture therapy (BNCT) exploits the nuclear reaction which occurs upon
irradiation of a 10 B nucleus located in a tumor cell with low energy neutrons. Fission of the boron
nucleus gives rise to an α particle and a recoiling 7 Li nucleus, the actual radiotherapic agents.
The short penetration length of these highly ionizing particles (5-9 µm, less than a typical cell
diameter) ensures that the damage is confined to the cells where fission events take place, thus
endowing BNCT with the potential to become a very selective form of radiotherapy. [1]
Delivering high doses of boron to tumor tissues in a selective fashion is key to the success of
BNCT. Boron-containing drugs investigated so far include boronated analogues of aminoacids
and nucleosides, functionalized boron clusters, antibody conjugates and T-cells loaded with
boron carbide nanoparticles. [2]
In this communication we discuss the development of novel boron delivery agents based on
organically modified silica nanoparticles. Silica nanoparticles provide an ideal scaffold for the
realization of biological and medical nanodevices: they are non-toxic and water soluble, they
accumulate preferentially in tumor tissues and are easily functionalized, for instance, with
imaging, targeting or shielding agents. These remarkable qualities make silica nanoparticles
excellent candidates for a prominent place in the next generation of boron carriers.
Mixed silicon and boron oxide nanoparticles containing a fluorescent dye were synthesized via
a modified Stöber method (ammonia catalyzed co-condensation of oxide precursors in alcohol)
and their toxicity, uptake and intracellular localization were studied.
These initial attempts were plagued by low boron loading and extensive boron leaching due to
the hydrolytic instability of the Si-O-B linkage. Two different routes were then investigated to
address these problems: modification of the oxide network in order to exclude water from the
interior of the nanoparticles, and replacement of the oxygen bridge with a more stable bridging
moiety. The former strategy involves the introduction of methyl groups into the oxide network
through the use of a mixture of suitable silicon precursors, while the latter relies on the selfcondensation
of a single precursor with pre-formed Si-(CH2)2-B bonds.
The efficacy of these two approaches will be discussed with respect to the boron loading and in
vitro behavior of the different kinds of nanoparticles.
[1] R.F. Barth et al., Clin Cancer Res, 2005, 11, 3987-4002
[2] G. Wu et al., Anti-Cancer Agents in Medicinal Chemistry, 2006, 6, 167-184
Screening of 1,3,4-oxadiazoles by narrow-bore HPLC with various
peptidomimetic calixarene-bonded stationary phases .
G. Bazylak a and A. A. Haidar b
PSA 10
a Department of Pharmaco-Bromatology, Faculty of Pharmacy, Collegium Medicum, Nicolaus
Copernicus University, Jagiellonska 13, 85-067 Bydgoszcz, Poland Tel: +4852 585 3915; Fax:
+4852 585 3817; E-mail: gbazylak@cm.umk.pl
b Al Khalil Pharmacy, Beirut 110236, Lebanon
Concave hydrophobic surface of the calixarene grafted silica can be treated as the valuable
peptidomimetic system for study of multiple associations between circulating drugs and serum
proteins. Thus, retention behaviour in series of 1,3,4-oxadiazoles with a potent analgesic activity
were determined in the narrow-bore isocratic and gradient HPLC systems employing
calix[6]arene-, calix[8]arene- as well as tert-butyl calix[4]arene-bonded stationary phases. When
acetonitrile + 2.65 mM phosphoric acid (55 : 45, v/v), pH* 3.25, mobile phase was applied
retention of these compounds increased with diminishing of their overall hydrophobicity
according to the general preference of more polar compounds by calixarene cavity in time of its
non-specific host-guest supramolecular interactions. The size of calixarene cavity and its upperrim
substitution slightly modified observed retention order, resolution and selectivity of
separation for oxadiazoles. Compare to retention on the highlyend-capped and polar-embedded
octadecylsilica HPLC columns an extended separation of some positional isomers of
halogenated oxadiazoles were observed on the used calixarenetype HPLC supports. In addition
formation of the 1:1 inclusion host-guest complexes between each calixarene-type stationary
phase and oxadiazoles were studied with MM+ and AM1 molecular modelling methods. The
structural and energetic factors leading to the hydrogen bond stabilized inclusion complexes
between mentioned species were considered and used for explanation of observed retention
sequence and separation selectivity of oxadiazoles in applied HPLC systems. The effect of
mobile phase components as acetonitrile and phosphate anion on deprotonation and monolayer
formation of silica-bonded calixarenes as well as their molecular recognition abilities in
developed HPLC procedures and previously reported PVC-based membrane electrodes [1] was
also discussed.
1] G. Bazylak, L.J. Nagels, H.J. Geise, Comb.Chem. & High Throughput Screen., 2004, 7, 345 .
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