Tailoring Magnetic Nanoparticles for Theranostic Applications

Funded by the Faculty of Natural Sciences, NTNU & the Department of Chemical Engineering, NTNU

This ongoing PhD project aims to develop nanoparticle-based delivery systems that combine magnetic iron oxide nanoparticles (IONPs) with therapeutic biomolecules — such as drugs or genes — inside stimuli-responsive polymeric shells, enabling magnetically guided, targeted release at the cell. Encapsulating such payloads in nanoparticles can improve accumulation at disease sites, reduce toxicity to healthy tissue, and improve pharmacokinetics compared to free-drug administration, but achieving this requires a detailed understanding of nanoparticle synthesis, encapsulation, and cellular interaction. The project is structured around three research activities.

The first research activity focuses on synthesizing IONPs via thermal decomposition and rendering them hydrophilic through phase transfer. Comparing three common iron precursors — iron(III) oleate, iron pentacarbonyl, and iron acetylacetonate — showed that iron acetylacetonate produced the most crystalline, strongly magnetic Fe₃O₄ nanoparticles (81 Am²/kg), albeit with solvent instability during synthesis, while iron oleate offered better control over particle size and shape at the cost of mixed-phase, lower-magnetization particles, and iron pentacarbonyl gave markedly weaker magnetic performance. Of four phase transfer strategies tested, none significantly altered the nanoparticles' physicochemical properties, but oxidative cleavage and base bath methods stood out for their simplicity and scalability, with selected particles showing promise as MRI contrast agents. Complementary work has also examined silica coating of IONPs as an alternative surface-engineering route: co-condensing the silica precursor TEOS with the amine-functional silane APTES produced discrete, rounded shells (unlike the fused, irregular shells from TEOS alone), and a systematic study across spherical and cubic cores established how the TEOS:APTES ratio and particle loading govern shell thickness, surface charge, and core architecture — providing design rules for tuning silica-coated IONPs to specific biomedical needs.

The second research activity aims to encapsulate IONPs together with biomolecules inside stimuli-responsive polymeric shells using flash nanoprecipitation (FNP), optimizing solvent, polymer, and process conditions to control loading, encapsulation efficiency, and release behavior. As part of this effort, the project has systematically studied how polymer concentration, solvent choice, and flow rate govern the size of PLGA nanoparticles formed by FNP, identifying a strong, mixing-independent solvent effect (with particle size varying more than threefold across solvents) attributed to molecular-level solvent–antisolvent interactions. An empirical scaling law, later refined using principal component analysis of solvent properties, now predicts nanoparticle size from polymer concentration and flow rate with high accuracy (R² = 0.99) — a step toward using PLGA-based FNP as a scalable, low-cost alternative to lipid nanoparticle systems for nucleic acid and drug delivery.

The third research activity, still ahead, will investigate how the resulting nanoparticle systems interact with cells — including uptake mechanisms with and without magnetic guidance (magnetofection), and how release efficiency can be enhanced through magnetic hyperthermia and stimuli-responsive shell design — with the goal of benchmarking performance against viral and other commercial delivery vectors.

Together, these research activities aim to build a rational, characterization-driven framework for designing magnetically responsive, polymer-encapsulated nanoparticle platforms for efficient and targeted biomolecule delivery.