Design and characterisation of casein coated and drug loaded magnetic nanoparticles for theranostic applications.

Theranostic systems enable early cancer diagnostic and treatment. In this work, we prepared Na-caseinate coated magnetic nanoparticles (MNP) to assess their capability as a theranostic system. This system enables monitoring by magnetic particle imaging (MPI), drug delivery and magnetic hyperthermia. MNP were synthesized in a continuous flow, coated with Na-caseinate and enzymatically crosslinked with transglutaminase to increase their colloidal stability and enable drug loading. They were investigated concerning their magnetic behaviour by DC magnetization measurements (DCM), magnetic particle spectroscopy (MPS) and AC-magnetometry to evaluate their suitability for MPI and hyperthermia. Further, their stability in different salt solutions as well as their encapsulation efficiency with a hydrophobic model drug (nile red), cell viability and uptake were investigated. Our results show that the Na-caseinate coating of MNP marginally effects the magnetic behaviour of the MNP with a consistent magnetization saturation M S of 109(5) A m 2 per kg(Fe) for uncoated and casein coated MNP and with a decrease of <15% of A 3 *, but only a slight decrease of 2% of A 5 / A 3 for Na-caseinate coated MNP. Furthermore, the Na-caseinate coating of MNP increased their salt stability, under unchanged magnetic behaviour. Drug loading (up to ∼75%) and release kinetics such as the delivery into cutaneous squamous cell carcinoma cells (SCL-1) was shown. Our results demonstrate that casein coated MNP are highly promising candidates for theranostic applications in drug delivery, magnetic hyperthermia and magnetic particle imaging.