Iron Oxide Nanoconstructs for the Ablation Therapy in Diseased Tissues: Systemic Analysis and Rational Design

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. In this work the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs) are studied. These nanoparticles are operated under a broad range of AMF conditions. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue > 42°C) and thermal ablation (Ttissue > 50°C) are derived in terms of particles concentrations, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles. Moreover, Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been achieved with the same nanoparticle. In the attempt to optimize and fully employ their potentiality in a single particle formulation, magnetic nanoconstructs are obtained by confining multiple, nanocubes within a polymeric (deoxy-chitosan) matrix. The resulting nanoconstructs – Magnetic NanoFlakes (MNFs) – exhibit a hydrodynamic diameter of 156 ± 3.6 nm, with a polydispersity index of about 0.2, and are stable in PBS up to 7 days. Upon exposure to an alternating magnetic fields they provide a specific absorption rate (SAR) about 60-fold than the single Nanocubes alone. The same nanoconstructs provide a remarkably high transversal relaxivity of 500 (mM s)-1, comparable with the hghest values avaiable in the current literature. Moreover, MNFs in phisiological relevant flow conditions shown potentials in magnetic targetted using an external static magnet. The MNFs represent a first step towards the realization of nanoconstructs with superior relaxometric and ablation properties for more effective theranostics.