Design and evaluation of amine-functionalized salicylic acid loaded hollow mesoporous silica nanoparticles for treatment of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous malignancy characterized by the absence of estrogen, progesterone, and HER2 receptors, limiting effective targeted treatment options. In this research, we investigated the anticancer activity of salicylic acid (Sa) encapsulated through hollow mesoporous silica nanospheres (HMSN). Molecular docking was initially done to assess the interaction of Sa with the major apoptotic and proliferative targets and found considerable binding affinities that imply anticancer activity. In accordance with these in silico results, Sa was encapsulated into HMSN effectively to produce Sa@HMSN, and the formulation was characterized for physicochemical properties using SEM, TEM, particle size, XRD, FTIR, Zeta potential, and BET analysis. An effective drug load and pH-dependent release mechanism was observed in HMSN. In vitro cytotoxicity was evaluated against MDA-MB-231 cells by MTT assay, exhibiting a dose-dependent inhibition of cell viability, with Sa@HMSN exhibiting significantly higher efficacy compared to free Sa or blank HMSN. Morphological observation revealed cellular shrinkage and membrane blebbing in treated cells. Ao/EtBr dual staining indicated apoptosis, with the Sa@HMSN treated cells showing chromatin condensation and nuclear fragmentation. Further, the expression of p53 was analyzed through immunocytochemistry. The findings indicate that Sa@HMSN are a promising nanotherapeutic platform for TNBC therapy, coupling predictive docking analysis with high in vitro efficacy.