Functional Nanoparticles (NPs) in Medicine

Funded By NTNU Health, NTNU Rectorate, Faculty of Natural Sciences, NTNU, Particle Engineering Centre (PEC), NTNU, Faculty of Medicine and Health Sciences, NTNU

This cross-disciplinary project focuses on the synthesis, functionalization, and application of tailor-made nanoparticles for biomedical use, spanning diagnostics and therapeutics. By combining controlled synthesis with advanced surface engineering and application-driven testing, the project aims to develop versatile nanoparticle platforms for sensing, imaging, targeted delivery, and biomolecule extraction.

One focus has been the controlled synthesis of silica-coated magnetic nanoparticles via a modified Stöber method. A full factorial design of experiments varied solvent type, iron oxide-to-silica precursor ratio, ammonium hydroxide concentration, and surface chemistry, and assessed their effects on particle size, morphology, and magnetic saturation. Maintaining dispersion pH above or below the nanoparticles' isoelectric point proved key to producing smaller, spherical particles, while the silica precursor's structure influenced morphology and surface amine availability for later functionalization. A time-resolved study of the reaction further clarified the underlying growth mechanism, informing the design of silica-coated nanoparticles for diagnostic and therapeutic use.

A second direction explored scalable production of functional nanocomposites via in-situ polymerization and flash nanoprecipitation (FNP). In-situ polymerization of acrylic acid on iron oxide nanoparticles was investigated as a cost-effective alternative to commercial SPRI bead kits for nucleic acid extraction; the amount of monomer used, which governs the reaction's initial pH, proved critical to polymerization kinetics, particle size, and surface functionality, yielding an extraction technology matching or exceeding commercial performance. Separately, FNP was used to encapsulate iron oxide nanoparticles in PLGA carriers for magnetically triggered drug release. Comparing nanoprecipitation and FNP showed mixing strongly affected nucleation and growth — successful encapsulation occurred only outside the Ouzo domain, at high polymer concentration and fast mixing, without compromising magnetic properties — leading to a surfactant-free method for producing stable PLGA–iron oxide nanocomposites for stimuli-responsive delivery.

The project further investigates nanomachinery for sensing, imaging, and targeting in living systems, using two complementary platforms. Mesoporous silica and silica-coated iron oxide nanoparticles were synthesized via biphasic stratification, with optimized conditions yielding 45–120 nm particles with 2–5 nm pores suited to drug loading. These carriers efficiently loaded doxorubicin, with release triggered by an alternating magnetic field to enable combined chemotherapy and magnetic hyperthermia. Complementing this, citrate-stabilized gold nanoparticles were synthesized via the Turkevich method and grown to 53 nm through a semi-continuous, seed-mediated approach, using residual citrate to drive growth in a single step; boiling conditions gave better size and morphology control than 70°C, yielding monodisperse particles whose plasmon-tunable optical properties support cellular sensing and imaging.

Another area compared thermal decomposition of iron oxide nanoparticles from three precursors — iron(III) oleate, iron pentacarbonyl, and iron acetylacetonate. Iron acetylacetonate gave the most crystalline, magnetic Fe₃O₄ nanoparticles (81 Am²/kg) despite solvent instability; iron oleate offered better size and morphology control but mixed-phase, lower-magnetization particles; and iron pentacarbonyl gave markedly weaker magnetic performance. Of four phase transfer strategies tested, none significantly altered particle properties, but oxidative cleavage and base bath methods stood out for their simplicity and scalability. Selected phase-transferred nanoparticles showed promise as MRI contrast agents, offering practical guidance for tailoring these nanoparticles for delivery and extraction applications.

Through these integrated activities, the project aims to establish advanced nanoparticle platforms with tunable properties, scalable production routes, and strong potential for next-generation biomedical diagnostics and therapies.