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Design of theranostic nanoparticles for cancer treatment functionalised by Layer-by-Layer assembly

Alberto Girelli

Design of theranostic nanoparticles for cancer treatment functionalised by Layer-by-Layer assembly.

Rel. Gianluca Ciardelli, Piergiorgio Gentile, Chiara Tonda Turo, Irene Carmagnola. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2020

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Cancer is considered among the leading causes of death each year worldwide, with an estimated 13.2 million deaths in 2030 for a global population of 8.3 billion people. To increase the survival rate, researchers focused on developing theranostic systems at the nanoscale, combining therapeutic compound with imaging tools in the same platform, improving drug delivery, pharmaco-kinetics, bio-distribution. In this work, we have investigated the design of an innovative theranostic nanoparticle capable to combine the SPIONs multimodal capabilities (MRI bio-imaging, magnetic targeting and hyperthermia) with more efficient and targeted drug release, exploiting Layer-by-Layer assembly (LbL) technique, using the SPION as a core. LbL technology has been studied in different contexts such as electronic, optical, biological and medical, thanks to its simplicity and versatility. It consists in the deposition of charged layers by alternating positive and negative polyelectrolytes. These layers attribute different wettability and biocompatibility characteristics to the functionalized surface. In this investigation we wanted to exploit the LbL technique as means to load the anticancer drug and through the layers degradation, to control the kinetics release. The nanoparticle was designed to combine the biocompatibility standards requirements set by the Food and Drug Administration (FDA), in order to exceed the steps 1-5 provided (Discovery and Development, Preclinical Research, Clinical Research, FDA Drug Review, FDA Post-Market Drug Safety Monitoring) up to the platform marketing. It was chosen to use bottom-up strategy for this compilative study of the nanoparticle design. SPIONs, composed of Fe3O4 and &#947;-Fe2O3, was selected as core due to its good cytocompatibility as reported in literature. Recent works showed the SPIONs average size is approx. 20 nm by TEM images. It has been reported that the SPIONs has characterised by a surface charge (measured by of Z-potential) ranging between -4 / + 23 mV. The surface charge was assumed to be essential for the deposition of subsequent layers. A deep investigation on the potential polyelectrolytes to be used in the LbL assembly were considered: Chitosan and Alginate among the natural polymers, Poly (allylamine hydrochloride) (PAH) and Polystyrene sulfonate (PSS) among the synthetics. Natural polymers have been selected for their high biomimetic properties, cytocompatibility and, also, widely approved by the FDA. PSS/PAH are the most biocompatible and the widely used among synthetic polymers; they are available at low cost and in large quantities. Literature reports their degradation in acid environment (pH<7) can consider them as pH-responsive polyelectrolytes. The pairs of bilayers investigated showed dimensions around 200 nm and external Z-potential between -50/+33 mV, suggesting to exploit passive targeting and EPR effect. Paclitaxel and Docetaxel are the most commonly used drugs in cancer therapy and those proposed in this study. Finally, it has been considered how to improve the circulation time and the target properties of this nanoparticles. “Stealth” characteristics to the immune system could be given by the external hydrophilic PEG on the shell, able to increase circulation times in blood environment. The amine groups expressed by the PEG can be exploited to graft specific antibodies (HER-2, EGFR, Biotin, HA) for the most common tumors (liver, prostate, lung, breast) by implementing active targeting.

Relators: Gianluca Ciardelli, Piergiorgio Gentile, Chiara Tonda Turo, Irene Carmagnola
Academic year: 2019/20
Publication type: Electronic
Number of Pages: 101
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/14984
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