Synthesis and In Vitro Biological Evaluation of a Second-Generation Multimodal Water-Soluble Porphyrin-RAPTA Conjugate for the Dual-Therapy of Cancers

Abstract

In this study we report the synthesis and biological evaluation of a novel cationic porphyrin-[Ru(η 6 -arene)(C2O4)PTA] (RAPTA) conjugate with potential as a multimodal dual-therapeutic agent. In the absence of high intensity light, relative to untreated cells our conjugate resulted in a 83% decrease in viable human adenocarcinoma cells at a concentration of 10 μM, which is significantly more active than the 57% decrease achieved with the same concentration of the unconjugated RAPTA complex alone. With a light dose of 20 J cm -2 (400 -1200 nm) a reduction 2 of 98% of viable cells was observed for the same concentration of conjugate. The conjugate is internalized by HT-29 cancer cells as proven by ICP-MS analysis and fluorescence microscopy: the latter result suggesting that the conjugate has applications as a multimodal agent by acting as a fluorophore to obtain in vivo biodistribution data. Furthermore, the conjugate has an excellent relative singlet oxygen quantum yield, and the tetrapyrollic unit was found to be photostable under irradiation by either white light or red light.

RAPTA‐Decorated Polyacrylamide Nanoparticles: Exploring their Synthesis, Physical Properties and Effect on Cell Viability

“…The concentrations of RAPTA‐PANPs administered were based on the amount of RAPTA bound to the nanoparticles as previously determined by ICP‐MS analysis, allowing for a direct comparison between conjugated and unconjugated nanoparticles – administering equivalent quantities of NH 2 ‐PANPs allowed for direct comparison to evaluate if the anticancer properties were a function of the presence of the RAPTA complex. Treatment with 2 gave a typical dose–response profile as reported previously by Sandland et al [25] . NH 2 ‐PANPs appeared to have a minimal effect on cell viability (IC 50 >500 μM).…”

“…(Scheme 1, Scheme 2). Previous studies have demonstrated that 2 is associated with an IC 50 >500 μM when incubated with HT‐29 for 24 hours [25] …”

“…starting from commercially available materials to yield a cytoactive RAPTA species with a conjugatable carboxylic acid functional group [24] . 2 was synthesised according to the method reported by Sandland et al [25] . (Scheme 1, Scheme 2).…”

Homo‐ and Hetero‐dinuclear Arene‐Linked Osmium(II) and Ruthenium(II) Organometallics: Probing the Impact of Metal Variation on Reactivity and Biological Activity

“…Synthesis:[ Ru(h 6 -3-(p-tolyl)propanoic acid)PTA(C 2 O 4 )] (S1), [36] silver oxalate [42] and tert-butyl (2-aminoethyl)carbamate [43] were prepared according to literature procedures. Complex 6a was prepared as described by Sandland et al [44] 3-(4-Methylcyclohexa-1,4-dien-1-yl)propanoic acid:4 -Methylcinnamic acid (predominantly trans)( 21.54 g, 132.8 mmol) was added to as olution of NH 3 (1 L) and EtOH (100 mL) cooled at À78 8C, followed by further EtOH (100 mL). The resulting colourless solution was stirred with am echanical stirrer followed by the addition of lithium (8.51 g, 1.23 mol) piecewise (ca.…”

“…Synthesis : [Ru(η 6 ‐3‐( p ‐tolyl)propanoic acid)PTA(C 2 O 4 )] ( S1 ), silver oxalate and tert ‐butyl (2‐aminoethyl)carbamate were prepared according to literature procedures. Complex 6 a was prepared as described by Sandland et al …”