Caffeine-Loaded Mesoporous Silica Nanoparticles as a Dual-Pathway Therapeutic Strategy in Benzene-Induced Acute Myeloid Leukemia

Breakthroughs in nanoscience have sparked a radical rethinking of how therapeutically valuable natural compounds are applied in medicine. This investigation seeks to engineer a nanoformulated natural product for potent cancer therapy. Toward this end, mesoporous silica nanoparticles (MSNPs) were prepared, thoroughly characterized, and then loaded with caffeine to construct a site-specific drug carrier, referred to as caffeine-coated nanoparticles (CcNPs). Computational docking simulations were performed to probe the binding affinity of the CcNPs to a panel of apoptotic protein targets, followed by in vitro and in vivo biological evaluations using relevant animal models. Free caffeine, the nano-encapsulated caffeine formulation, and doxorubicin were each introduced intravenously into a benzene-initiated AML rodent model. Anti-leukemic activity was assessed by blood profiling, enzymatic biomarker quantification, and RT-PCR-based analysis of molecular shifts in leukemic markers. The docking data indicated potent intermolecular binding between CcNPs and apoptotic regulators. In vitro findings revealed antioxidant effects of clear statistical significance, while in vivo results indicated a return to baseline expression levels of the leukemic markers STMN1 and S1009A, along with the re-establishment of normal blood cell morphology and hematological parameters in animals receiving the nano-therapy. A parallel marked recovery in hepatic and kidney function markers was also recorded. In addition to these effects, the nano-formulation restored aberrantly high GAPDH and mTOR expression driven by benzene to physiological levels. The treatment further diminished pro-survival signaling through the NF-kappa B cascade and lifted P53 expression. With respect to the TRAIL axis, it enhanced the expression of the death-promoting factors TRAIL and DR5 while suppressing the anti-apoptotic mediator cFLIP. The body of evidence indicates that caffeine-laden MSNPs, designated CcNP/nanomedicine, can suppress the expansion of transformed cells and activate the cell-death-promoting TRAIL pathway to counteract benzene-driven leukemia. These observations establish our nano-therapeutic as a remarkably promising interventional option for AML.