Rapid Eradication of Human Breast Cancer Cells through Trackable Light-Triggered CO Delivery by Mesoporous Silica Nanoparticles Packed with a Designed photoCORM

The surprising discovery of salutary effects of low doses of carbon monoxide (CO) in mammalian physiology has raised intense research interest in CO delivery to biological targets under controlled conditions. In recent attempts, photoactive metal carbonyl complexes (photoCORMs) have been employed to trigger CO release at the target sites. In this work, a designed photoCORM namely, fac -[Re(CO) 3 (pbt) (PPh 3 )](CF 3 SO 3 ) ( 1, pbt =2-(2-pyridyl)benzothiazole) has been synthesized and characterized by spectroscopic methods and crystallography. This photoCORM not only releases CO upon illumination with low-power UV light (305 nm, 5 mW cm –2 ) but also exhibits a “turn-off” of its orange luminescence (λ em = 605 nm) upon release of one CO ligand. The latter property provides a convenient way to track the CO release event. The photoCORM 1 has been entrapped within the pores of the narrow channels of 100 nm mesoporous Al-MCM-41 nanoparticles and the loaded {Re-CO}@Al-MCM-41 MSNs have been characterized by powder X-ray diffraction (PXRD), FTIR spectroscopy and chemical analysis. Results of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and the SEM-EDX elemental maps of C, Si, O, Re, and P confirm that the carbonyl complex is retained within the pores of the MSNs. Strong electrostatic binding of the cationic photoCORM to the negatively charged walls of the Al-MCM-41 nanoparticles results in very little leaching of the CO donor from the host matrix. The hydrodynamic parameters (155 nm diameter in PBS, ζ-potential = −28.53 ± 1.00 mV) of the biocompatible {Re-CO}@Al-MCM-41 MSNs fall in the right range of the drug-carriers and the particles are readily endocytosed by MDA-MB-231 (human breast cancer) cells. The entry of the {Re-CO}@Al-MCM-41 MSNs into the cellular matrix is easily visualized by the intense orange luminescence (λ ex = 400 nm) of the loaded cells. Short exposure of the cells to low-power UV light brings about a rapid diminution of the orange luminescence due to CO release from the photoCORM locked within the MSNs and causes CO-induced death of the cancer cells. Recently, CO has been shown to induce apoptotic death in different types of cancer cells as well as enhance the efficacy of cancer chemotherapy. The simple design of the {Re-CO}@Al-MCM-41 MSNs and their response to light allows for the first time to deliver the drug (CO) from a pro-drug locked within a biocompatible MSNs that can readily accumulate within malignant sites due to the “enhance permeability and retention” (EPR) effect. In addition, the CO delivery process can be conveniently tracked through the loss of luminescence of the MSNs.