Del Genio, Valentina (2022) Peptide-based dynamic nanovectors for anticancer and antimicrobial drugs. [Tesi di dottorato]

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Item Type:	Tesi di dottorato
Resource language:	English
Title:	Peptide-based dynamic nanovectors for anticancer and antimicrobial drugs
Creators:	Creators Email Del Genio, Valentina valentina.delgenio@unina.it
Date:	5 July 2022
Number of Pages:	116
Institution:	Università degli Studi di Napoli Federico II
Department:	Farmacia
Dottorato:	Scienza del farmaco
Ciclo di dottorato:	34
Coordinatore del Corso di dottorato:	nome email D'Auria, Maria Valeria mariavaleria.dauria@unina.it
Tutor:	nome email Galdiero, Stefania UNSPECIFIED Chourpa, Igor UNSPECIFIED
Date:	5 July 2022
Number of Pages:	116
Keywords:	Drug delivery; Nanovectors; Peptides; Anti-cancer; Anti-microbial.
Settori scientifico-disciplinari del MIUR:	Area 03 - Scienze chimiche > CHIM/03 - Chimica generale e inorganica Area 03 - Scienze chimiche > CHIM/08 - Chimica farmaceutica
Date Deposited:	22 Jul 2022 09:49
Last Modified:	28 Feb 2024 11:07
URI:	http://www.fedoa.unina.it/id/eprint/14373

Collection description

Biomedical research devotes a huge effort to develop novel nanovectors for sustainable and controlled delivery of drugs, to augment their therapeutic effectiveness and to achieve personalized medicine. This PhD thesis is focused on the development of peptide-based nanovectors that can be used in various situations, namely to deliver anticancer drugs or antimicrobial drugs. The introduction presents the concept of nanotechnology, a science that stimulates important innovations in the medical and healthcare treatments. Through the control of materials at the nanoscale level, it is possible to produce nanovectors able to protect drugs from degradation, to modulate pharmacokinetics, to enhance intracellular penetration and intracellular distribution while reducing undesired secondary effects. The introduction describes drug delivery strategies aimed at improving the specificity of current therapeutic approaches, in particular through the use of peptides. Then there are two main sections devoted respectively to the anti-cancer and anti-microbial nanovectors. Section 1 is focused on the design, synthesis and characterization of new generation of self-assembling nanovectors based on peptides and designed for stimuli-responsive release of drugs. Peptide self-assembly is governed by noncovalent interactions that can be modulated by varying the amino acid sequences and manipulating the environmental parameters. Decorated on their surface with a cell-penetrating peptide gH625, the nanovectors shown and enhanced uptake in cancer cells. The superparamagnetic iron oxide nanoparticles (SPION) were additionally included in the formulation, to (i) favour accumulation in target tissues with help of external magnetic field and (ii) follow their biodistribution by MRI. Section 2 describes the use of peptides for the development of drug delivery tools useful for antimicrobial applications. In particular, we obtained several analogues of an antiviral peptide developed in our laboratory against Herpes Simplex Virus type 1. The obtained peptide analogues were characterized by the presence of a PEG-Cholesterol moiety which favours the interaction with the membrane bilayer of the target cell and enhances the anti-microbal activity. These results were further exploited to develop a carrier based on the use of a Janus dendrimer functionalized with two different antiviral sequences. Finally, we also designed nanovectors made of silver nanoparticles which combine the action of both silver ions and of an antimicrobial peptide indolicidin and demonstrate an enhanced antibacterial activity and a lower cyto- and endo-toxicity.

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