NANOMATERIAL-BASED THERAPEUTICS FROM THE HOST TO THE GUEST: CANCER THERAPY AND MICROBIOME INTERVENTION

The course belongs to the PhD course in Bio and Nanomaterials Science and Technology, which aims to develop materials and techniques in the frame of chemical-physical-biological analyses useful for the development of bio- and nanotechnologies. In this context, the course provides to the students the knowledge on the application of bionanomaterials to cancer therapy.

The students are guided in the understanding of the actual strategies to deliver chemo- and targeted-therapies in cancer patients by mean of nanomaterials. Analysing the history of chemo- and target-therapies together with drug delivery, human microbiome composition, strategies for microbiome intervention in cancer therapy, the students acquire the rationale of the key steps pursued by scientists to overcome actual biological barriers and the misunderstanding and pitfalls that are still there.

Basic knowledge of nanomaterials, molecular and cellular biology.

Parte I (15 hours)
• Chemotherapy – a historical overview with examples focused on the development and application of nitrogen mustard, folic acid, vinca alkaloids, taxanes and cisplatin.
• Target therapies - the development and application of Imatinib, Gefitinib and Bevacizumab
• Hallmarks of cancers - an analysis of the principles, which govern cancer complexity: Sustaining proliferative signalling, Evading growth suppressors, Resisting cell death, Enabling replicative immortality, Inducing angiogenesis, Activating invasion and metastasis, Reprogramming energy metabolism and Evading immune destruction.
• Barriers in drug delivery – principles of nanomedicine and the biological barriers: passive vs active targeting, the mononuclear phagocyte system, nonspecific distribution of nanoparticles, hemorheological limitations, intratumoral pressure, cell membrane internalization, endosomal escape and multi drug resistance mechanisms.
• Misunderstandings and pitfalls - common mistakes and underestimations in nanoparticle testing: nanoparticles extravasion, tissue penetration and formulation; difference between mouse models and human; approaches to metastatic cancer; personalized therapy.
• Doxil, a history of success - rational for the development of a liposomal drug: Slow drug release, Site avoidance, Accumulation in the tumor, Protein binding, RES clearance, Glomerular filtration, Microvasculature permeability, Extravascular transport; Stealth technology and Remote loading; Applications in clinic.
• CRISPR/CAS9 technology – a historical overview; bacterial CRISPR-CAS systems; CRISPR technology in human; Applications and limitations in cancer.
• RNA Therapeutics - a historical overview and the important achieved milestones

Part II (15hours)
• Human microbiome: Overview of microbiome composition; diversity of human microbiotas; the central rule of gut microbiome; microbiome-host coevolution; microbiome in health and diseases;
• Gut microbiome-organ axis: gut-brain axis, gut-skin axis; gut-vagina axis, gut-liver axis, gut-lung axis;
• Based therapeutics for microbiome intervention: prebiotics, probiotics, postbiotics, fecal microbial transplantation;
• Targeting the gut and tumor microbiota in cancer, gut oncomicrobiome signatures associated with cancer diagnosis, tissue-based and tumor-based microorganisms
• Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections
• Biogenesis of nanoparticles from producer bacterial strains
• Nanotechnology intervention of the gut microbiome for cancer therapy: nanotechnology manipulating microbiome metabolites, nanotechnology for microbiome modulation, microbe-inspired nanotechnologies, challenges and perspective
• In vitro, in vivo and ex vivo models to study tumor-microbiome interaction and microbiome intervention for human diseases

All the didactic materials will be provided by the teacher. There is no book for this course.

The assessment of learning takes place by means of a short oral presentation. The objective of the exam consists in verifying and evaluating the ability of the student to include at least one content of the course in her/his current PhD research project. The students must demonstrate a critical thinking and the ability to expose the topic in a formal and concise manner using an appropriate scientific language. The constant and active participation to the lessons will be considered in the final evaluation.

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Teaching is organized in frontal theoretical lectures. PowerPoint slides will be used during the lessons. The teaching material is present and downloadable from the University's Moodle e-learning platform.

Questo insegnamento tratta argomenti connessi alla macroarea "Capitale umano, salute, educazione" e concorre alla realizzazione dei relativi obiettivi ONU dell'Agenda 2030 per lo Sviluppo Sostenibile