CO-Induced apoptotic death of colorectal cancer cells by a luminescent photoCORM grafted on biocompatible carboxymethyl chitosan

Abstract

A photo-active luminescent rhenium carbonyl complex namely, [Re(CO)3(phen)(pyAl)](CF3SO3) was grafted on a biocompatible carboxymethyl chitosan (CMC) matrix through Schiff base condensation reaction. The light-induced CO delivery from ReCMC has been shown to eradicate human colorectal adenocarcinoma cells (HT-29) very efficiently in a dose-dependent fashion. The onset of CO-induced apoptosis was realized by caspase-3,-7 detection aided by fluorescence confocal microscopy. ReCMC represents a unique example of a biocompatible and biodegradable antineoplastic agent that could find its use in cancer photopharmacology.

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

“…In the absence of illumination to induce CO release, complex 4 shows no apparent cellular toxicity. However, a dose dependent eradication of HT‐29 cells was observed upon UV light‐induced CO release …”

“…No cytotoxicity data were reported for 1–3. Complex 4, [Re(CO) 3 (phen)(pyAl)]O 3 SCF 3 (where pyAl=pyridine‐4‐carboxaldehyde), which was grafted on to a biocompatible carboxymethyl chitosan (CMC) matrix, was found to be taken up by MDA‐MB‐231 breast cancer cells and HT‐29 colon cancer cells as evidenced by intracellular emission at 550 nm . In the absence of illumination to induce CO release, complex 4 shows no apparent cellular toxicity.…”

“…This method has been explored by Mascharak and coworkers using Re(I)-based photoCORMs. [17] Each Re(I) complex shown in Figure 3 exhibits an emission in the range of 500-620 nm. Complexes 1-4 release CO in the presence of low-power UV light (5 mW/cm 2 ; centered at 302 nm), with the number of CO molecules released (1-3) depending on the monodentate ligand in the axial position.…”

“…Complexes 1-3 were studied in terms of cellular uptake and intracellular distribution within human metastatic breast adenocarcinoma cells (MDA-MB-231) prior to CO release using confocal microscopy ( Figure 4). [17] All showed cytosolic distribution except [Re(CO) 3 (PPh 3 )(phen)]O 3 SCF 3 (2, Figure 4) which was also identified to accumulate in nuclei. [17a] No cytotoxicity data were reported for 1-3.…”

Diminished viability of human ovarian cancer cells by antigen-specific delivery of carbon monoxide with a family of photoactivatable antibody-photoCORM conjugates

“…1 In recent years, exogenous delivery of CO has shown promise as a novel therapeutic in a variety of disease and injury models, including cancer. 2 The challenge of delivering efficacious concentrations of CO to a target tissue has been approached by our group and others by synthesizing CO-releasing molecules (CORMs) with properties necessary for a potential therapeutic, including water solubility, 3 incorporation within biocompatible materials 4,5 and controllable release of CO. [6][7][8][9] Very recently, with the use of photoactivatable CORMs (photoCORMs) our group has elucidated mechanism(s) by which CO exerts deleterious effects against human breast and ovarian cancer cell models. 10,11 In such studies we have observed sensitization of ovarian cancer cells to drugs like cisplatin and paclitaxel through coadministration of CO. 11 Because sensitization to conventional chemotherapeutics could mitigate the poor outcome of ovarian cancer treatment, precise target-specic delivery of CO to the malignant tissue appears to be a very desirable goal.…”