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Tesi etd-04272017-111230

Type of thesis
Perfezionamento
Author
GRILLONE, AGOSTINA FRANCESCA
URN
etd-04272017-111230
Title
Smart nanomaterials to overcome highly invasive tumor resistance
Scientific disciplinary sector
ING-IND/34
Course
INGEGNERIA - Biorobotics
Committee
relatore Prof. DARIO, PAOLO
Keywords
  • drug delivery system
  • magnetic nanoparticles
  • nanoceria
  • Tumor
Exam session start date
;
Availability
completa
Abstract
The aim of this PhD Thesis has been the investigation of nanotechnological solutions for cancer therapy. In particular, hybrid nanomaterials composed by both inorganic and organic components have been synthesized, characterized, and in vitro studied, demonstrating their potentialities for biomedical application. <br>In the first part of the thesis magnetic solid lipid nanoparticles (Mag-SLNs) have been proposed as nanocarriers for the targeted delivery of sorafenib, a chemotherapeutic agent exploited for the treatment of hepatocarcinoma, and nutlin-3a, a potent non-genotoxic drug candidate for the cure of the glioblastoma multiforme.<br>Concerning Mag-SLNs as nanovectors for sorafenib some promising results have been obtained. Developed nanoparticles showed to inhibit the proliferation of cancer cells due to cytotoxic action of the encapsulated drug, and to localize this effect in a desired area thanks to possibility of controlling their movement/targeting through ax external magnetic field. Therefore, such characteristic makes Mag-SLNs extremely attractive, because it would allow to overcome the problem of lack of selectivity of traditional chemotherapy. A preliminary investigation about relaxivity properties, moreover, demonstrated that Mag-SLNs present superior features with respect to other commercially-available system, and therefore can be exploited as negative contrast agents in diagnostic imaging.<br>About Mag-SLNs for encapsulation of nutlin-3a, in vitro studies clearly showed superior antitumor activity of drug-loaded nanoparticles respect to free drug. Obtained results demonstrated that such nanovectors represent an ideal system to optimize the delivery of the drug into tumor cells, thus enhancing therapeutic index of nutlin-3a. A blood-brain-barrier in vitro model was also developed to allow future studies of nanoparticle crossing of the barrier and of tumor cells targeting, at level of which the action of the drug will be potentiated by magnetic nanoparticles-mediated hyperthermia.<br>In the final part, we will propose the use of a liposomal drug delivery system for the encapsulation of cerium oxide nanoparticles (nanoceria), a powerful nanotechnological tool for the regulation of the free radical level in the biological environment, and thus extremely useful in all those cases where oxidative stress play a key role, including cancer. Nanoceria-loaded liposomes resulted stable, biocompatible, and they retain strong antioxidant activities, resulting a promising platform for the targeted delivery of the nanoparticles.<br><br>
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