Biomimetic mesoporous silica nanoparticles for drug delivery in a synthetic lethality approach

Biomimetic mesoporous silica nanoparticles for drug delivery in a synthetic lethality approach. In the recent years, the scientific community has payed a growing attention on nanotechnology, which is the use of materials with a dimension range in the nanometer size. In particular, the application of nanotechnology in medicine, “Nanomedicine”, is increasingly important, because the small size of nanomaterials allows their easy interactions with biomolecules and cells. Furthermore, nanomaterials have several physical and chemical features that can be used in different medical fields, such as imaging, therapy and drug delivery. Concerning the drug delivery, the Nanoparticles (NPs) with pores of different size are of particular interest, thanks to their high cargo capability, high surface area and the possibility to functionalize the surface for several purpose. For instance, the use of NPs brings numerous benefits in cancer therapy, currently consisting in the use of chemotherapy drugs, alkylating agents and enzymatic inhibitors that are not specific for the tumour mass, but also affect healthy organs. Thus, it is necessary to increase the drug dosage needed to be effective on the cancer cells, but at the same time the side effects for the patients increase. NPs allow to carry a small amount of drug, localized in the target organ, obtaining a controlled release, an improved pharmacokinetic profile and side effects’ decrease. Mesoporous Silica Nanoparticles (MSN), that belong to the category of ceramic nanoparticles, are receiving huge attention due to their biocompatibility, mechanical strength, resistance to microbial attack and to enzymatic degradation in a physiological environment. Furthermore, they have a large surface area and pores volume, which allow to upload a large amount of drug; also, the pores can be capped by gatekeepers that avoid the overflow of the cargo before reaching the target. Thus, MSN can be a valid support to the already existing therapeutical solutions against the cancer improving their efficacy. In this master thesis work, the attention has been focalised on the Multiple Myeloma which is a disease belonging to the monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. MSN with a surface functionalized by amino-groups (-NH2) have been synthesized and then their carrying efficacy has been evaluated to verify the possibility to use them as nanocarrier for AGI-6780, an inhibitor of mutant IDH2 /R140Q.