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