Anisotropic Growth Method for Constructing Stimulus-Responsive Janus Composite Nanoparticles for Dual-Drug Delivery in Tumor Therapy

In this study, we used an interfacial energy-mediated, anisotropic growth method to synthesize rod-shaped, periodic mesoporous organosilica (PMO) on the surface of the mesoporous silicon-titanium composite nanoparticles (MSTNs) with a core-shell structure, resulting in sphere-rod structured, Janus composite nanoparticles (MSTNs/PMO). Adjusting the amount of surfactant and the solvent ratio (water/ethanol) in the reaction system allowed for the fabrication of MSTNs/PMO nanoparticles with diverse morphologies, and their growth mechanism was analyzed systematically. The MSTNs/PMO surface was functionalized with amino and thiol groups to facilitate the loading of doxorubicin (DOX) and tetrandrine (TET). Then, folic acid (FA) was grafted onto the drug-loaded nanoparticles (MSTNs/PMO-DOX/TET-FA). This step successfully constructed a stimulus-responsive combinatorial dual-drug delivery system. MSTNs/PMO-DOX/TET-FA exhibited high loading efficiencies, reaching 26.54% for DOX and 6.37% for TET. Drug release studies demonstrated significant pH-responsive release behavior and sequential release characteristics of the system. Cytotoxicity and cellular uptake assays revealed that the system exhibited excellent biosafety and significant targeting ability toward tumor cells. Collectively, these findings suggested that the dual-drug delivery system has potent antitumor therapeutic efficacy and offered a viable strategy for synergistic tumor therapy.