Hollow-degree-tuned Prussian blue–mesoporous silica nanoplatforms for chemo-photothermal cancer therapy with preliminary microfluidic perfusion evaluation

Background Balancing photothermal performance and drug-delivery capacity remains a key challenge in the structural design of multifunctional nanomedicines. Hollowing can increase internal space for drug accommodation but may simultaneously reduce the amount of NIR-absorbing Prussian blue (PB), creating an inherent trade-off between drug-delivery capacity and photothermal performance. Methods The hollow state of hollow mesoporous Prussian blue (HMPB) nanocubes was regulated by controlled HCl etching, followed by a common mesoporous silica (mSiO 2 ) coating, to generate low-, intermediate-, and high-hollow formulations. The resulting formulations were evaluated for physicochemical properties, photothermal performance, doxorubicin (DOX) loading and release, cellular response, intracellular fluorescence, chemo-photothermal interaction, and preliminary microfluidic perfusion performance. Results Increasing hollowing enhanced DOX loading from 525 to 867 μg⋅mg −1 and promoted drug release, but progressively reduced photothermal performance. The measured photothermal conversion efficiencies of 1-, 2-, and 3-HMPB@mSiO 2 were 23.37%, 18.62%, and 14.41%, respectively. ICP-MS showed decreasing Fe contents with increasing hollowing, while PB-equivalent-mass-matched measurements yielded similar photothermal conversion efficiencies (16.80%, 15.80%, and 14.41%), indicating that PB abundance is a major contributor to the observed photothermal differences. DOX release was enhanced by both mild acidity and mild hyperthermia relative to pH 7.4/37 °C. After treatment-matched correction for nanoparticle-related optical interference, the blank carriers showed limited acute carrier-associated cytotoxicity in HeLa cells over 24 h, and quantitative fluorescence imaging confirmed effective intracellular DOX delivery. At an equal total formulation concentration, the intermediate-hollow 2-HMPB@mSiO 2 -DOX formulation produced the strongest combined therapeutic response. Multi-dose combination-index, Bliss-independence, and Loewe-additivity analyses further supported increasingly synergistic chemo-photothermal interactions with increasing treatment effect. Preliminary syringe-pump-driven microfluidic perfusion in physiological medium preserved the principal structure-dependent trends in particle dispersion, drug leakage, and NIR heating. Conclusion These results demonstrate that hollow-state engineering provides a practical strategy for balancing competing photothermal and drug-delivery functions in PB-based nanoplatforms.