Polyelectrolyte complex templated synthesis of monodisperse, sub-100 nm porous silica nanoparticles for cancer targeted and stimuli-responsive drug delivery

Porous silica nanoparticles (PSiNPs) have long attracted interest in drug delivery research. However, conventional synthesis methods for sub-100 nm, functionalised PSiNPs typically give poor monodispersity, reproducibility, or involve complex synthetic protocols. We report a facile, reproducible, and cost-effective one-pot method the of cancer targeting pH responsive this size range, without need post-synthetic modification. This was achieved by using monodisperse l-arginine (Arg)/ poly(acrylic acid) (PAA) polyelectrolyte complexes (PECs) as soft templates silane hydrolysis condensation. Highly uniform with tunable control between 42 178 nm disordered pore structure (1.1–2.7 nm) were obtained. Both PAA Arg retained within PSiNPs, which enabled high doxorubicin hydrochloride (Dox) loading capacity (22% w/w) 4-fold increase release under weakly acidic compared to physiological pH. The surface presentation conferred significantly higher intracellular accumulation Arg/PAA-PSiNPs patient-derived glioblastoma cells non-tumorigenic neural progenitor cells, effectively translated lower IC50 values Dox-loaded than non-functionalised PSiNPs. work brings forward new insights development highly desirable built-in functionalities biomedical applications.