Folate-engineered mesoporous silica-encapsulated copper (II) complex [Cu(L)(dppz)]+: An active targeting cell-specific platform for breast cancer therapy

A novel metal complex (mononuclear copper(II) complex [Cu(L)(dppz)]+ (LH = 2-[(2 dimethylaminoethylimino)methyl]phenol, coordinated ligand, dppz = dipyrido[3,2-a:2′,3′-c]phenazine) was encapsulated in a nanovector (FA@MSNPs) to produce an efficient targeted delivery platform. [Display omitted] •A novel metal complex (mononuclear copper(II) complex [Cu(L)(dppz)]+ (LH = 2-[(2 dimethylaminoethylimino)methyl]phenol, coordinated ligand, dppz = dipyrido[3,2-a:2′,3′-c]phenazine) was encapsulated in a FA@MSNPs, to produce an efficient targeted delivery platform.•The developed FA@MSNPs is nontoxic up to a concentration of 100 μg/mL, and it is specifically taken up by breast cancer cells through FA receptor-mediated targeting.•The [Cu(L)(dppz)]+ loaded MSNPs produced breast cancer cell death primarily by apoptosis whereas they are not toxic to normal breast epithelial cells. Aspects of inorganic medicinal chemistry aim at developing metal coordinated complexes that are efficient therapeutic agents for cancer. However, intrinsic toxicity of these complexes impedes their effective clinical use. In order to reduce the toxicity and improve the pharmacokinetics and biodistribution, we developed a nanovector candidate and encapsulated in it a metal complex (mononuclear copper(II) complex [Cu(L)(dppz)]+ (LH = 2-[(2-dimethylaminoethylimino)methyl]phenol, coordinated ligand, dppz = dipyrido[3,2-a:2′,3′-c]phenazine) which is an efficient targeted delivery platform based on folate-receptor. The in-vitro cytotoxicity of (FA@MSNPs-[Cu(L)(dppz)]+) to the breast cancer cells MCF-7 and MDA-MB-231, and normal breast epithelial cell HBL-100 have been evaluated. The complex (FA@MSNPs-[Cu(L)(dppz)]+), compared to free [Cu(L)(dppz)]+, is highly cytotoxic to the breast cancer cells, in view of its efficient cellular uptake, and the delivery is mediated by FA receptor which produced only negligible cytotoxicity to the normal breast epithelial cell, HBL-100. Also, the mechanism of breast cancer cell death brought about by [Cu(L)(dppz)]+ loaded mesoporous silica nanoparticles (MSNPs) is primarily apoptosis whereas they are not toxic to normal breast epithelial cells. Hence, folate-conjugated MSNPs encapsulated with [Cu(L)(dppz)]+ has potential to be developed as a target-specific drug for breast cancer. This metal complex-loaded platform opens up newer opportunities to accommodate multiple metal-based drugs for cell-specific cancer therapy.