Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes

Abstract

Iron(III) complexes [FeL(B)] ( 1 – 4 ) of a tetradentate phenolate-based ligand (H 3 L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido [3,2- a :2′,3′- c ]-phenazine (dppza in 1 ), ( N -dipyrido[3,2- a :2′,3′- c ]-phenazino)amidobiotin (dppzNB in 2 ), dipyrido [3,2- a :2′,3′- c ]-phenazine-11-carboxylic acid (dppzc in 3 ) and 2-((2-biotinamido)ethyl) amido-dipyrido[3,2- a :2′,3′- c ]-phenazine (dppzCB in 4 ) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near −0.7 V versus saturated calomel electrode in dimethyl sulfoxide–0.1 M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

Iron(III) Complexes of Vitamin B6 Schiff Base with Boron‐Dipyrromethene Pendants for Lysosome‐Selective Photocytotoxicity

“…The cytotoxicity was measured from the IC 50 values (50 % inhibitory concentration) obtained from the cell‐viability assay. The complexes generally show significant photocytotoxicity in the cancer‐cell lines and are negligibly toxic in dark conditions (Table , Figures S12–S16) . The IC 50 values of the control complex 1 , in 400–700 nm light, are > 100 µ m in all of the cell lines.…”

“…The values are taken from refs , . and are converted to µ m using the approximate molecular mass of Photofrin® (600 g mol –1 ); at 633 nm excitation with a fluence rate of 5 J cm –2 .…”

“…The cellular localization pattern of fluorescent complex 3 (10 µ m ) in HeLa cells was visualized using a confocal microscope. Standard experimental procedures were adopted for cell plating and post treatment processing . To understand the subcellular localization of the complex, HeLa cells were incubated with the complex (10 µ m ) for 4 h in the dark.…”

Synthesis, Characterization, and Biological Evaluation of Red-Absorbing Fe(II) Polypyridine Complexes

“…Worthy of note, the same group also synthesized bimetallic Fe(III) complexes as PSs in view of DNA cleavage [46,47] and site specific protein cleavage [48]. Additionally, a recent publication by the same authors showed that the conjugation of a phototoxic Fe(III) complex to biotin allows for selective tumor delivery of the PDT agent [49]. In comparison to complexes with a +3 oxidation state, the studies of Fe complexes with a +2 oxidation state as a PS are scare.…”

Biotin-Conjugated Multilayer Poly [D,L-lactide-co-glycolide]-Lecithin-Polyethylene Glycol Nanoparticles for Targeted Delivery of Doxorubicin

“…Specifically, PLGA was chosen as the hydrophobic core for its biodegradable and biocompatible nature, along with its promising ability to encapsulate high amount of hydrophobic drugs (which has been approved by Food and Drug Administration [FDA] as the nanomaterial) 17 ; lecithin was selected as a monolayer around the PLGA core to enhance the encapsulation ability and biocompatibility of PLGA NP; DSPEePEGeCOOH could be inserted into the lecithin monolayer to form a PEG shell, then to enhance the stability of PLGA NP by producing both steric hindrance and electrostatic repulsion, and prolong the circulation time of PLGA NP in vivo; DSPE-PEG-biotin, a novel targeting ligand, was used for both active targeting of tumor cells thanks to the presence of biotin because biotin is a small molecular weight ligand known to target the sodium-dependent multivitamin transporter (SMVT) on the tumor cells, 18,19 and extending the duration in circulation system, thanks to the presence of PEG chains known to decrease the recognition by the immune system. 20 Profoundly, it has been reported that SMVT transporters are overexpressed in many tumor cells including HepG2 cells. [21][22][23] Thus, the cell experiments in this study were exerted on HepG2 cells.…”