title: M2L4 coordination capsules with tunable anticancer activity upon guest encapsulation.
abstract: Metallosupramolecular cages and capsules have gained increasing popularity as both molecular containers and anticancer agents. For successful combination of these properties a thorough analysis of the effect of guest encapsulation on the host's cytotoxic properties is highly required. Here we report on the cytotoxicity modulation of Pt(ii) and Pd(ii)-linked M2L4 coordination capsules upon encapsulation of guest molecules such as pyrene and caffeine. The anticancer activity of the capsules against various human cancer cells (HT-29, T-24, HL-60 and its resistant counterparts HL-60/Dox and HL-60/CDDP) significantly altered upon the guest encapsulation. The encapsulation of pyrene molecules causes a decrease in the cytotoxicity of the Pt(ii) capsule, which is stronger than that of the Pd(ii) capsule. The cytotoxicities of the caffeine containing capsules are lower than that of the empty capsules (except for HL-60), but still superior to cisplatin under the same conditions. The observed trends in the anticancer activity of the capsules and their host-guest complexes correlate with their different stabilities toward glutathione, estimated by NMR-based kinetic experiments. Mechanistic insights into the observed cytotoxicities are obtained by fluorescence microscopy imaging of tumor cells treated with the capsules and their pyrene complexes. The data suggest the glutathione-triggered disassembly of the capsular structures as a potential activation pathway for their cytotoxicities.
authors.affiliation: Faculty of Chemistry and Pharmacy, University of Sofia, 1, J. Bourchier blvd., Sofia 1164, Bulgaria. Ahmedova@chem.uni-sofia.bg.
authors.forename: Anife
authors.initials: A
authors.lastname: Ahmedova
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, Sofia 1000, Bulgaria.
authors.forename: Rositsa
authors.initials: R
authors.lastname: Mihaylova
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, Sofia 1000, Bulgaria.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Momekova
authors.affiliation: NMR Laboratory, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 9, Sofia 1113, Bulgaria.
authors.forename: Pavletta
authors.initials: P
authors.lastname: Shestakova
authors.affiliation: Faculty of Chemistry and Pharmacy, University of Sofia, 1, J. Bourchier blvd., Sofia 1164, Bulgaria. Ahmedova@chem.uni-sofia.bg.
authors.forename: Silviya
authors.initials: S
authors.lastname: Stoykova
authors.affiliation: Faculty of Chemistry and Pharmacy, University of Sofia, 1, J. Bourchier blvd., Sofia 1164, Bulgaria. Ahmedova@chem.uni-sofia.bg.
authors.forename: Joana
authors.initials: J
authors.lastname: Zaharieva
authors.affiliation: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. yoshizawa.m.ac@m.titech.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashina
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, Sofia 1000, Bulgaria.
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.affiliation: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. yoshizawa.m.ac@m.titech.ac.jp.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Akita
authors.affiliation: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. yoshizawa.m.ac@m.titech.ac.jp.
authors.forename: Michito
authors.initials: M
authors.lastname: Yoshizawa
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002110:Caffeine / Q000737:chemistry / Q000494:pharmacology; D002214:Capsules; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D056831:Coordination Complexes; D011721:Pyrenes; D002110:Caffeine; D010984:Platinum; D010165:Palladium; C030984:pyrene; D007770:L-Lactate Dehydrogenase; D005978:Glutathione