Highly-fluorescent BODIPY-functionalised metallacages as drug delivery systems: synthesis, characterisation and cellular accumulation studies

被引：10

作者：

Aikman, Brech ^{[1
]}

Bonsignore, Riccardo ^{[1
,2
]}

Woods, Ben ^{[3
,4
]}

Doellerer, Daniel ^{[5
]}

Scotti, Riccardo ^{[1
]}

Schmidt, Claudia ^{[1
]}

Heidecker, Alexandra A. ^{[6
,7
]}

Poethig, Alexander ^{[6
,7
]}

Sayers, Edward J. ^{[8
]}

Jones, Arwyn T. ^{[8
]}

Casini, Angela ^{[1
,9
]}

机构：

[1] Tech Univ Munich, Dept Chem, Chair Med & Bioinorgan Chem, Lichtenbergstr 4, D-85748 Garching, Germany

[2] Univ Palermo, Dipartimento Sci & Tecnol Biol Chim & Farmaceut, Viale Sci,Edificio 17, I-90128 Palermo, Italy

[3] Birkbeck Univ London, Sch Sci, Inst Struct & Mol Biol, Malet St, London WC1E 7HX, England

[4] Birkbeck Univ London, Sch Sci, Dept Biol Sci, Malet St, London WC1E 7HX, England

[5] Univ Groningen, Stratingh Inst Chem, Nijenborgh 4, NL-9747 AG Groningen, Netherlands

[6] Tech Univ Munich, Catalysis Res Ctr, Ernst Otto Fischer Str 1, D-85748 Garching, Germany

[7] Tech Univ Munich, Dept Chem, Chair Inorgan & Met Organ Chem, Ernst Otto Fischer Str 1, D-85748 Garching, Germany

[8] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Cardiff CF10 3NB, S Glam, Wales

[9] Tech Univ Munich, Munich Data Sci Inst, D-85748 Garching, Germany

来源：

DALTON TRANSACTIONS | 2022年 / 51卷 / 19期

关键词：

GAUSSIAN-BASIS SETS; ATOMS LI; CAGES; ENDOSOME; RELEASE; BINDING; PROTEIN; DRIVEN; EEA1; TOOL;

D O I：

10.1039/d2dt00337f

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

With the aim of designing new metallosupramolecular architectures for drug delivery, research has focused on porous 3-dimensional (3D)-metallacages able to encapsulate cytotoxic agents protecting them from metabolism while targeting them to cancer sites. Here, two self-assembled [Pd2L4](4+) cages (CG1 and CG2) featuring 3,5-bis(3-ethynylpyridine)phenyl ligands (L) exo-functionalised with dipyrromethene (BODIPY) groups have been synthesised and characterised by different methods, including NMR spectroscopy and mass spectrometry. H-1 NMR spectroscopy studies shows that the cages are able to encapsulate the anticancer drug cisplatin in their hydrophobic cavity, as evidenced by electrostatic potential (ESP) analysis based on XRD studies. The stability of the cages in an aqueous environment, and in the presence of the intracellular reducing agent glutathione, has been confirmed by UV-visible absorption spectroscopy. The luminescence properties of the cages enabled the investigation of their cellular uptake and intracellular localisation in human cancer cells by confocal laser scanning microscopy. In melanoma A375 cells, cage CG1 is taken up via active transport and endocytic trafficking studies show little evidence of transport through the early endosome while the cages accumulated in melanosomes rather than lysosomes. The antiproliferative activity of the lead cage was investigated in A375 together with two breast cancer cell lines, SK-BR-3 and MCF7. While the cage per se is non-cytotoxic, very different antiproliferative effects with respect to free cisplatin were evidenced for the [(cisplatin)(2)subset of CG1.BF4] complex in the various cell lines, which correlate with its different intracellular localisation profiles. The obtained preliminary results provide a new hypothesis on how the subcellular localisation of the cage affects the cisplatin intracellular release.

引用

页码：7476 / 7490

页数：15