Self-assembled silibinin-containing phosphazene/cystamine hybrid nanospheres as biodagradable dual-drug carriers with improved anticancer activity on a breast cancer cell line

Abstract

In this study, pH and redox sensitive biodegradable PPZs@Silibinin polymeric nanospheres were synthesized by the polymerization reaction of Hexachlorocyclotriphosphazene (HCCP), Cystamine dihydrochloride (CA) and the anticancer drug Silibinin as monomers. Later designed as a therapeutic system, this nano drug-carrier was also loaded with Doxorubicin (Dox), a type of cancer drug. As a result, a drug self-delivery system (DSDS) was developed, which had the property of biodegradation in tumor tissues thanks to the redox active disulfide bonds in its structure from pH-sensitive nanospheres containing two anticancer drugs. Biodegradation-associated in vitro release of cancer drug (Dox) from the Dox loaded PPZs@Silibinin nano drug-carrier was performed in the presence of glutathione (GSH) at pH 6.5 and pH 7.4. While 93.06% Dox release was observed in pH 6.5 medium containing 10 mM GSH in 24 h, this value was 56.60% in pH 7.4 + 10 mM GSH medium. In addition, clonogenic analysis and cytotoxicity studies were performed on the MDA-MB-231 cell line to determine the anticancer properties of PPZs@Silibinin loaded with Dox. It was determined that PPZs@Silibinin@Dox nanospheres containing 20.5 nM Dox for 0.75 µL are highly effective in MDA-MB-231 cells than free Dox.