Work

Design and Biodistribution of PEGylated Core–Shell X-ray Fluorescent Nanoparticle Contrast Agents

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Nanoparticle (NP) uptake by macrophages and their accumulation in undesired organs such as the liver and spleen constitute a major barrier to the effective delivery of NPs to targeted tissues for bioimaging and therapeutics. Surface functionalization with polyethylene glycol (PEG) has been demonstrated to be a promising strategy to limit NP sequestration, although its longitudinal stability under physiological conditions and impact on the NP biodistribution have not been investigated with an in vivo quantitative approach. X-ray fluorescence (XRF) imaging has been employed to noninvasively map the in vivo biodistribution of purposely designed molybdenum-based contrast agents, leading to submillimeter resolution, elemental specificity, and high penetration depth. In the present work, we design a stepwise layering approach for NP synthesis to investigate the role of chemisorbed and physisorbed PEG on silica-coated molybdenum-based contrast agents in affecting their in vivo biodistribution, using whole-body XRF imaging. Comparative quantitative in vivo studies indicated that physisorbed PEG (1.5 kDa) did not substantially affect the biodistribution, while the chemisorption route with mPEG-Si (6–9 PEG units) led to significant macroscopic variations in the biodistribution, leading to a reduction in NP uptake by the liver. Furthermore, the results highlighted the major role of the spleen in compensating for the limited sequestration by the liver, microscopically validated with a multiscale imaging approach with fluorophore doping of the silica shell. These findings demonstrated the promising role of XRF imaging for the rapid assessment of surface-functionalized contrast agents with whole-body in vivo quantitative pharmacokinetic studies, establishing the groundwork for developing strategies to identify and bypass undesired NP uptake.

Source: ACS Applied Materials & Interfaces

DOI: 10.1021/acsami.5c01902

Authors: Giovanni M. Saladino, Bertha Brodin, Mihai Ciobanu, Nuzhet I. Kilic, Muhammet S. Toprak, Hans M. Hertz

Institutions: KTH Royal Institute of Technology, Stanford University

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500