Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity

Abstract

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, [Mn­(CO)3(Imdansyl)­(L1)]­(CF3SO3) (1) (where L1 = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to [Mn­(CO)3(Imdansyl)­(L2)]­(CF3SO3) (2) (where L2 = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM 1 in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue 2.

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

“…Indeed, photoactive metal carbonyl compounds able to release CO (known as photoCORMs) have gained momentum over the past few years regarding their potential use against cancer [20][21][22]. In vitro experiments, conducted by the group of Mascharak [23][24][25][26], have shown that manganese-based complexes bearing azopyridine-type ligands could eradicate about 40% of an MDA-MB-231 breast cancer colony at a concentration of 75 μM upon visible light irradiation [27]. Similarly, about 50% of cell death occurred under light exposure of the compound fac-[MnBr(CO 3 (pbt))] at 100 μM (where pbt =2-(2-pyridyl)benzothiazole), which could be tracked intracellularly following the light-induced release of its pbt ligand [28].…”

A red light‐activable MnI(CO)3‐functionalized gold nanocomposite as the anticancer prodrug with theranostic potential

“…The k CO value was determined from the linear fit of the plot (Figure S33); the apparent first‐order rate constant of photoinduced CO release by the hybrid was determined to be as high as 33.7 × 10 −3 s −1 , which was substantially greater than the CO release rate of complex 1 and those of other photoCORMs (Table S5). [ 31–43,74 ] The facile interelectronic delocalization between AuNPs' surface and the Mn(I) complex was likely responsible for the observed enhancement of the CO release rate. The collective effect of 657 number of Mn(I) complexes functionalizing and individual AuNP also contributed to the increased rate of CO release.…”

“…[ 15–30 ] The salutary effect of a low dose of CO has prompted research on the photoactivated release of exogenous CO from CO‐releasing molecules (CORMs) with spatial and temporal resolution for clinical applications, including cancer therapy. [ 31–48 ] However, the delivery, tumor specificity, and retention of CORMs in malignant tumors are formidable challenges in utilizing photoCORMs for cancer therapy. [ 42 ]…”

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The salutary effect of a low dose of CO has prompted research on the photoactivated release of exogenous CO from CO-releasing molecules (CORMs) with spatial and temporal resolution for clinical applications, including cancer therapy. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] However, the delivery, tumor specificity, and retention of CORMs in malignant tumors are formidable challenges in utilizing photoCORMs for cancer therapy. [42] Gold nanoparticles (AuNPs) and gold nanorods have emerged as ideal drug-delivery platforms because of their easy synthesis, large surface areas, good biocompatibility, and tunable and facile functionalization.…”

Cytotoxicity of Mn-Based photoCORMs of Ethynyl-α-Diimine Ligands Against Different Cancer Cell Lines: The Key Role of CO-Depleted Metal Fragments

“…In vitro experiments, conducted by the group of Mascharak [22][23][24][25], have shown that manganesebased complexes bearing azopyridine-type ligands could eradicate about 40% of an MDA-MB-231 breast cancer colony at a concentration of 75 µM upon visible light irradiation [26]. Similarly, about 50% of cell death occurred under light exposure of the compound fac- [MnBr(CO3(pbt)] at 100 µM, which could be tracked intracellularly following the light-induced release of its 2-(2pyridyl)benzothiazole (pbt) ligand [27].…”