Superparamagnetic iron oxide nanoparticles loaded in hybrid lipid/polymer nanoparticles as a multifunctional platform to treat brain cancer

Some aggressive cancers may be difficult to treat because of the topology and drug resistance. Brain tumours like glioblastoma multiforme present complexity in being treated with conventional chemotherapeutic drugs because of the presence of the blood-brain barrier. During the last years, nanomedicine showed promising results in the treatment of this kind of diseases. It combines medicine with nano-engineering in order to generate systems able to accomplish tasks otherwise difficult to achieve, such as accurate and targeted drug delivery and on demand therapy administration. It pledges incredible improvements with respect to older techniques for early diagnosis and high-resolution imaging. Nanoparticles are structures with all three physical dimension under few hundreds nm. These can be tailor made and engineered quite easily in order to accomplish several tasks all at once. Nanoparticles are also employed for drug delivery purposes, since they show a prolonged circulation half-life, reduced non-specific uptake, increased tumor accumulation through passive or active targeting. Moreover, they are able to encapsulate a significant amount of drug and deliver it in hostile environment. The delivery of conventional drugs can also be coupled with other therapies, like hyperthermia, to enhance the therapeutic efficiency. Hybrid lipid-polymer NPs arranged in a core-shell fashion combine chemical stability of liposomes in aqueous environment with the high structural strength of polymers. During the last years such systems have proven to be one of the best candidate for drug delivery, and if loaded with magnetic nanoparticles and exposed to alternate magnetic field they could combine hyperthermia and chemotherapy treatment enhancing the effectiveness of antitumoral therapies. The biodegradable polymeric core that encapsulates the drug molecule allows the delivery of hydrophobic drugs. The lipidic shell coated with polyethylene glycol provides biocompatibility in a biological environment, stealth effect towards the immune system (in particular the Reticuloendothelial system) and steric stabilization. A polymeric core is preferred to a lipidic one because of the higher structural strength, narrower size distribution and ease of synthesis procedure. It also allows a controlled release profile when heated above the glass transition temperature by the encapsulated superparamagnetic Iron-oxide nanoparticles. The aim of this work is to analyze through a bibliographic research the best methods, materials and systems to develop a multifunctional delivery platform. The latter should be able to deliver the chemotherapy drug to the target site and at the same time trigger local hyperthermia to enhance the effectiveness of chemotherapeutic drug and also trigger apoptosis in GBM cells. In order to optimize the stability of nanovectors, the release profile and the size distribution here we comapre two synthesis procedure: emulsion/evaporation and nanoprecipitation. Moreover to further improve the effectiveness of these systems, here we investigate physical principles behind hyperthermia generation through SPIONs, that are single domain magnetic crystal already approved for biomedical application by FDA and EMA. Through this physical digression it would be more clear how the heat rises and thus it would be easier to improve such magnetic systems to achieve therapeutic level of SAR and combine effectively the hyperthermia with chemotherapy.