Abstract
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 for the synthesis of cancer targeting and pH responsive PSiNPs in this size range, without the need for post-synthetic modification. This was achieved by using monodisperse l-arginine (Arg)/ poly(acrylic acid) (PAA) polyelectrolyte complexes (PECs) as soft templates for silane hydrolysis and condensation. Highly uniform PSiNPs with tunable size control between 42 and 178 nm and disordered pore structure (1.1–2.7 nm) were obtained. Both PAA and Arg were retained within the PSiNPs, which enabled a high doxorubicin hydrochloride (Dox) loading capacity (22% w/w) and a 4-fold increase in drug release under weakly acidic pH compared to physiological pH. The surface presentation of Arg conferred significantly higher intracellular accumulation of Arg/PAA-PSiNPs in patient-derived glioblastoma cells compared to non-tumorigenic neural progenitor cells, which effectively translated to lower IC50 values for Dox-loaded Arg/PAA-PSiNPs than non-functionalised PSiNPs. This work brings forward new insights for the development of monodisperse PSiNPs with highly desirable built-in functionalities for biomedical applications.
Highlights
Porous silica nanoparticles (PSiNPs) are amongst the most promising vehicles for drug delivery
polyelectrolyte complex (PEC) formed from poly(acrylic acid) (PAA) and NH4+ in mixed water–ethanol solvents have been extensively used as templates to give hollow silica nanoparticles (HSNPs) [16,17,18,19]
The hydrodynamic diameters and zeta-potentials of the PECs and Porous Silica Nanoparticle (PSiNP) were determined by dynamic light scattering (DLS) using the Zetasizer Nano equipped with a He-Ne laser and with scattered light detected at 173(Malvern Instrument Ltd., Worcestershire, UK)
Summary
Porous silica nanoparticles (PSiNPs) are amongst the most promising vehicles for drug delivery. Particle size and morphological control is achieved though varying reagent concentrations, reaction temperature, and pH This method does not typically allow the synthesis of highly uniform sub-100 nm particles, which are optimal for prolonged blood circulation, tumour accumulation, and enhanced cell uptake [4,5]. PECs formed from poly(acrylic acid) (PAA) and NH4+ in mixed water–ethanol solvents have been extensively used as templates to give hollow silica nanoparticles (HSNPs) [16,17,18,19] This method, typically leads to large particle sizes or poor polydispersity. We report a novel one-pot synthesis method to obtain monodisperse, sub-100 nm PSiNPs with intrinsic cancer targeting, efficient drug loading, and pH responsive drug release behaviour by exploiting the unique alcohol induced polyelectrolyte complexation of L-arginine (Arg) and PAA (Scheme 1). This study provides important insights for the reproducible, scalable, and costeffective synthesis of monodisperse, multifunctional PSiNPs through the judicious choice of polyelectrolyte templates to achieve cancer targeting and pH-responsive drug delivery to improve anti-cancer efficacy
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