Calcium phosphate nano-platform for nucleic acid delivery as a new tool in nanomedicine

Magnetic nanomaterials (MNPs) have attained significant interest in a wide range of applications, including imaging, catalysis, nanofluids, colloidal photonic crystals, data storage, optical filters, defect sensing, and environmental remediation. Moreover, MNPs also have a potential use in biomedical applications, such as regenerative medicine and nano-medicine, leveraging on the smart functionalities enabled by magnetic properties—though such properties must be associated with low toxicity and appropriate physicochemical properties to enable use in vivo. Currently, the most widely used MNPs are based on iron, nickel, manganese, cobalt, gadolinium, and their compounds. Particularly, iron is categorized as a trace element within the human body and has the ability to undergo metabolism. Iron based MNPs for use in medicine are commonly referred to paramagnetic or superparamagnetic compounds, therefore exhibiting magnetic properties only when an external magnetic field is applied, and refer to two different general categories: (i) iron-oxide-based magnetic nanoparticles (SPIONs such as maghemite and magnetite) and (ii) iron-doped biocompatible and bioactive nanoparticles such as iron-doped hydroxyapatite. The iron oxides, together with those of gadolinium and manganese have also gained considerable attention in biomedical imaging (MRI), due to the feasibility of tailoring magnetic behavior. A wide range of materials such as ceramics, metals, polymers, and their composites, are utilized for developing MNPs for various biomedical applications. Recently, researchers have also paid significant attention to developing magnetic nanomaterial composites (MNCs) by combining two or more components to produce integrated nano-systems enabling bio-relevant multifunctional properties. From a material science perspective, the handling and synthesis of MNCs may be difficult due to the presence of impurities, the high tendency to agglomerate as well as the biocompatibility issue. MNPs, such as SPIONs, have attracted a lot of attention in the field of nanomedicine due to high superparamagnetic properties. Regarding their impact on cells, some potential adverse effects, such as the generation of reactive oxygen species (ROS) and the triggering of inflammatory responses under certain conditions, have been reported. The accumulation in vivo of SPIONs in some organs, such as the kidney and liver, has been documented as a long-term cytotoxicity problem. Such drawbacks raise complications in regulatory evaluations, so such kind of nano-composites may not reach the clinical application. In this respect, my Ph.D. project is focused to develop new solutions based on biocompatible and bioactive calcium phosphate, where magnetic properties are conferred by doping with iron, with the purpose to combine the material biodegradability and the ability to be magnetized by minimizing the cytotoxicity of nanomaterials like SPIONS. The research was carried out at the Institute of Science, Technology and Sustainability for Ceramics, belonging to the National Research Council of Italy (CNR-ISSMC) under the supervision of Dr. Anna Tampieri and Dr. Simone Sprio.