Fully Biodegradable Magnetic Micro-Nanoparticles: A New Platform for Tissue Regeneration and Theranostic

Abstract

Nowadays, magnetic materials are receiving special attention due to their potential applications in different fields and in particular in medicine. Magnetic micro-nano-particles have been progressively employed as support materials for enzyme immobilization, and have been used as drug-delivery vehicles, contrast agents for magnetic resonance imaging as well as heat mediators for hyperthermia-based anti-cancer treatments and many other exciting biomedical applications. Magnetic materials have also attracted a big interest in the field of bone tissue regeneration because it has been demonstrated that magnetic nanoparticles have effect of osteoinduction even without external magnetic force. Therefore, one of the most big challenge in this field is the production of magnetic materials with good biocompatibility and biodegradability. In fact, the long-term effects in the human body of iron oxide (maghemite or magnetite), the most popular magnetic phase used in medicine and biotechnology, are not yet completely assessed. To this aim, in this work we developed an innovative biocompatible and bioresorbable superparamagnetic-like phase by doping nano-hydroxyapatite with Fe2+/Fe3+ ions (FeHA). Moreover the same magnetic nanoparticles were used as nano-particulate emulsifier for the preparation of hollow hybrid Fe-HA-poly(L-lactic) acid (PLLA) micro-nano-spheres. PLLA has been used because poly(α-hydroxy-esters) are the most frequently used synthetic polymers for biomedical applications owing to their biocompatibility, hydrolytic degradation process and proper mechanical properties. These micro-nanospheres could be used as new type of scaffold for hard tissue regeneration. In fact, spherical scaffold display several advantages respect to the monolithic counterpart e.g., (i) improving control over sustained delivery of therapeutic agents, signalling biomolecules and even pluripotent stem cells, (ii) serving as stimulus-sensitive delivery vehicles for triggered release, (iii) introducing porosity and/or improve the mechanical properties of bulk scaffolds by acting as porogen or reinforcement phase, (iv) supplying compartmentalized micro-reactors for dedicated biochemical processes, (v) functioning as cell delivery vehicle, and, finally, (vi) giving possibility of preparing injectable and/or mouldable formulations to be applied by using minimally invasive surgery. Moreover, the same magnetic materials could find applications in nanomedicine as a multifunctional carrier. Their magnetic functionality could be utilized to move them into the body towards target organs by an external magnetic field. Furthermore, the superparamagnetic feature of the nanoparticles could allow to tailor the release of the therapeutic agent by switching (on-off) the external magnetic field and/or to treat cancer cells by hyperthermia.