International Summer School PROGRAM - Laboratoire d'Infochimie ...

Controlled and Targeted Drug Delivery Using Supramolecular System
Vladimír Král a,b , Jarmila Králová c , Martin Havlík b,c Kamil Záruba b , Pavel
Řezanka b , Zdeněk Kejík b , Tomáš Bříza b,d , Robert Kaplánek b,d , Pavel Martásek d
a Zentiva k.s., Part of the sanofi-aventis group, U Kabelovny 130, 102 37 Prague 10,
b Institute of Chemical Technology, Department Analytical Chemistry, Technická 5,
166 28 Prague 6, Czech Republic (email: vladimir.kral@vscht.cz),
c Institute of Molecular Genetics, AS CR, Flemingovo nam.2, Prague 6, Czech Republic,
d st
Charles University in Prague, 1 Faculty of Medicine, Kateřinská 32, Czech Republic.
Rational design of functional nanomaterials is of current interest because of a variety of
potential applications ranging from chemistry to biological sciences. One of the key
areas is selective drug delivery using supramolecular strategies. The uptake of
exogenous molecules such as drugs into cells can arise from a variety of mechanisms
that can be broadly classified as active and passive transport. Active uptake requires that
target molecules are recognized by specific intermolecular interactions, selected, and
shuttled across the cell membrane by receptors.
Porphyrin chemistry has undergone a renaissance over the past ten years due to
potential applications of these compounds in areas including supramolecular chemistry,
solar energy conversion and catalysis.
Here we describe application of porphyrin-conjugates for supramolecular targeted drug
delivery of cytostatic drugs and ODN in combination with photodynamic therapy.
Novel porphyrin-conjugates with oligoethyleneglycol, oligopeptide, alkaloid, mono-,
disaccharide, and cyclodextrin substitution showed significant binding properties as
well as photosensitizing potential in vitro and in vivo and displayed an increased
selectivity for malignant tissue. Moreover, polymethine and other polycationic
porphyrin derivatives exhibit not only very specific tumor localization, but also into-cell
antisense oligonucleotide transport properties as was demonstrated on the primary
leukemic cells.
Financial support from the Czech Grant Agency No. P303/11/1291, 203/09/1311,
P301/10/1426 and the Ministry of Education of the Czech Republic (projects No.
MSM6046137307 and LC06077) is gratefully acknowledged.