RESUMEN
Multicore magnetic iron oxide nanoparticles, nanoflowers (NFs), have potential biomedical applications as efficient mediators for AC-magnetic field hyperthermia and as contrast agents for magnetic resonance imaging due to their strong magnetic responses arising from complex internal magnetic ordering. To realise these applications amenable surface chemistry must be engineered that maintain particle dispersion. Here a catechol-derived grafting approach is described to strongly bind polyethylene glycol (PEG) to NFs and provide stable hydrogen-bonded hydrated layers that ensure good long-term colloidal stability in buffers and media even at clinical MRI field strength and high concentration. The approach enables the first comprehensive study into the MRI (relaxivity) and hyperthermic (SAR) efficiencies of fully dispersed NFs. The predominant role of internal magnetisation dynamics in providing high relaxivity and SAR is confirmed, and it is shown that these properties are unaffected by PEG molecular weight or corona formation in biological environments. This result is in contrast to traditional single core nanoparticles which have significantly reduced SAR and relaxivity upon PEGylation and on corona formation, attributed to reduced Brownian contributions and weaker NP solvent interactions. The PEGylated NF suspensions described here exhibit usable blood circulation times and promising retention of relaxivity in-vivo due to the strongly anchored PEG layer. This approach to biomaterials design addresses the challenge of maintaining magnetic efficiency of magnetic nanoparticles in-vivo for applications as theragnostic agents. STATEMENT OF SIGNIFICANCE: Application of multicore magnetic iron-oxide nanoflowers (NFs) as efficient mediators for AC-field hyperthermia and as contrast agents for MR imaging has been limited by lack of colloidal stability in complex media and biosystems. The optimized materials design presented is shown to reproducibly provide PEG grafted NF suspensions of exceptional colloidal stability in buffers and complex media, with significant hyperthermic and MRI utility which is unaffected by PEG length, anchoring group or bio-molecular adsorption. Deposition in the selected pancreatic tumour model mirrors liposomal formulations providing a quantifiable probe of tissue-level liposome deposition and relaxivity is retained in the tumour microenvironment. Hence the biomaterials design addresses the longstanding challenges of maintaining the in vivo magnetic efficiency of nanoparticles as theragnostic agents.