Spatio-temporal in vivo distribution of core-shell mesoporous silica nanoparticles by label-free X-ray fluorescence imaging

Abstract

Mesoporous silica nanoparticles (MSNs) have emerged as versatile drug delivery systems with promising applications in diagnostics and therapy. However, structural heterogeneity among MSNs and limited spatio-temporal tracking capabilities have resulted in inconsistent in vivo data, hindering the establishment of reliable pharmacokinetics, metabolism, and structure–activity relationships (SAR). Here, we report the design, synthesis, and interface engineering of a multilayered MSN (MoMSN) theranostic platform comprising a molybdenum (IV) oxide (MoO₂) core for intrinsic, label-free in vivo tracking via X-ray fluorescence (XRF) imaging, a fluorophore-doped silica layer for tissue-level visualization, and a mesoporous silica shell for potential drug delivery. Following comprehensive physicochemical characterization and in vitro safety assessment, the nanoparticles were intravenously administered to mice for multimodal imaging and biodistribution analysis. Whole-body XRF imaging revealed that MoMSNs exhibited rapid systemic turnover, with transient accumulation in the lungs followed by minimal retention in the liver and spleen. Immunofluorescence analysis confirmed confinement within major blood vessels and decreased macrophage uptake in the liver and spleen. Surface PEGylation further reduced organ retention as well as macrophage uptake. These findings demonstrate that surface chemistry strongly influences the in vivo fate of MSNs and that PEGylation promotes rapid clearance while minimizing uptake by the mononuclear phagocyte system. Importantly, this work establishes MoMSNs as an intrinsically traceable nanoplatform for quantitative whole-body tracking without external radiolabels, enabling more reliable evaluation of nanoparticle biodistribution and structure–activity relationships.