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

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.