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Targeted Nanocarriers for synergistic drug delivery to Multiple Myeloma

Federica Sidoti Abate

Targeted Nanocarriers for synergistic drug delivery to Multiple Myeloma.

Rel. Valentina Alice Cauda. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2024

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Abstract:

The aim of this Master Thesis work is to develop targeted nanocarriers for drug delivery acting as a synergistic anticancer therapy in Multiple Myeloma (MM). These drug-loaded nanocarriers, thanks to their surface functionalization, can selectively target cancer cells and be internalized by them, avoiding the high toxicity and other side-effects of conventional antitumor therapies. Two different kinds of nanocarriers have been developed: liposomes and lipid-coated Mesoporous Silica Nanoparticles (MSNs). Liposomes, which are spherical vesicles having at least one lipid bilayer, have been prepared using a thin film hydration method and extrusion, to obtain monodisperse suspensions of unilamellar vesicles (about 100 nm). The highly water-insoluble drug AGI-6780 has been encapsulated into the lipid bilayer of liposomes. The second nanoconstruct consists of a Mesoporous Silica Nanoparticle core coated with a self-assembled lipid bilayer (shell). Mesoporous silica is characterized by a good biocompatibility and a high specific surface area (approximately 1000 m2/g), which enables to load a great amount of drug. The Mesoporous Silica Nanoparticles have been synthetized using a template-assisted sol-gel self-assembly process, obtaining 40-50 nm nanoparticles with a mesoporous structure characterized by cylindrical pores (3-4 nm). Furthermore, both nanocarriers have been functionalized with antibody fragments. For this purpose, anti-CD38 monoclonal antibody was chosen by reason of CD38 receptors overexpression in MM cancer cells. AGI-6780 drug is not lethal for cells itself, but it has a synergistic effect with Carfizomib (CFZ), a common chemotherapy drug to which patients often develop resistance. In this context, it is envisioned to deliver the site-selective targeted nanocarriers with the encapsulated AGI drug to the patient while already administering, in a systemic way, the carfilzomib drug. First experiments in in-vitro cell culture of MM have been carried out to explore the correct dose and timing for the synergistic drug action at the Molecular Biotechnology Center (MBC, University of Turin).

Relatori: Valentina Alice Cauda
Anno accademico: 2023/24
Tipo di pubblicazione: Elettronica
Numero di pagine: 119
Soggetti:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: Nuovo ordinamento > Laurea magistrale > LM-21 - INGEGNERIA BIOMEDICA
Aziende collaboratrici: Politecnico di Torino
URI: http://webthesis.biblio.polito.it/id/eprint/30535
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