Abstract

Emodin (EO) is a naturally occurring anthraquinone with promising anticancer activity; however, its clinical application is limited by poor aqueous solubility and low bioavailability. Herein, we demonstrate that surface engineering of fluorescent SBA-15 nanocarriers governs the intracellular fate of EO by modulating drug confinement, release behavior, intracellular trafficking, and apoptotic responses. SBA-15 was functionalized with aminopropyl groups and a fluorescent moiety to generate traceable nanocarriers with distinct drug–carrier interactions. Physicochemical characterization (SAXS, BET, SEM/TEM, TGA, UV–Vis, and fluorescence spectroscopy) confirmed the preservation of the ordered mesoporous structure and efficient EO encapsulation (~35%). In PC3 prostate cancer cells, the functionalized system (SBA-15–M|EO) exhibited enhanced cytotoxicity (IC50 = 18.2 µM) compared to free EO and the non-functionalized carrier. Time-lapse fluorescence microscopy demonstrated efficient cellular uptake, perinuclear accumulation, and sustained intracellular release, whereas flow cytometry revealed distinct apoptotic responses. SBA-15|EO promoted rapid intracellular EO accumulation and extensive late apoptosis, while SBA-15–M|EO induced gradual intracellular accumulation accompanied by delayed but sustained apoptosis. Molecular docking further revealed favorable interactions of EO with the anti-apoptotic proteins BCL-2 and BCL-xL (ΔGbind≈ −6.5 kcal mol−1). These findings establish a direct relationship between nanocarrier surface chemistry, intracellular trafficking, and apoptotic fate, highlighting surface engineering as a strategy for controlling cellular responses beyond conventional drug delivery.

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