2sd Report IAEA: PREPARATION OF ALBUMIN AND GOLD/ALBUMIN NANO-PARTICLES BY RADIATION-INDUCED CROSS-LINKING

GRASSELLI, MARIANO; SILVIA ALONSO; FLORES, CONSTANZA Y.; ACHILLI, ESTEFANIA

2014-04-01/2017-05-01

22-30

Nanotecnologia

Tecnologia sanitaria y curativa-Varios

Breast cancer is the tumor with the highest incidence and mortality of women in the world; it is for this reason that many investigations are aimed to therapeutic drug design strategies for diagnosis and treatment. Tremendous advances have been made in the treatment, prevention and early detection of these malignancies; however none of the current therapies are specifically able to cover all the variants of this disease that differ in its histopathology characteristics and genomic and genetic variations [2.1]. For example, 90% of breast cancers without detectable metastases in lymphatic nodes are treated systemically with chemotherapy, although 70?80% of these patients will not develop distant metastasis and therefore suffer from the serious side-effects of this treatment [2.2]. Furthermore, many of the available drugs are not able to reach the site of metastases [2.3]. For this reason there is a new approach in the development of novel therapeutic strategies which allow high degree of specificity and spatial extent of the tumours even after metastasis spread. This approach is addressed by nanotechnology 2. [2.3]. The use of nanotechnology in medicine, also called nanomedicine, is based on the obtention generation of nanostructures, such as nanoparticles (NP), with particular physicochemical characteristics able to be easily detected and some therapeutic loads in the same structure, combining therapeutic and diagnostic functions. Additionally, these NPs have increased efficiency relative their containing therapeutic entity. They can be targeted to specific tumour tissues due to its pharmacokinetics, pharmacodynamics and enhanced intracellular activation. These characteristics depend on size and surface properties of the NPs. NPs size of currently used in anti-cancer therapy varies between 10?100 nm. An advantage of the use of NPs in such therapies is that the tumour vasculature has higher permeation for macromolecules, in addition to the poorly functionality of lymphatic system in the surround media, NPs accumulate in tumours leading to phenomenon known as ?Effect of enhanced permeability and retention? also called EPR [2.4, 2.5]. The surface of the NPs has a pivotal role in the fate within the body given by the interactions between it and the local environment. Furthermore, by the covalent attachment of targeting ligand gives rise to specific interactions between target cells and NPs. This functionality will allow the NP to enter the cell via receptor-mediated endocytosis. There are different types of NPs according to their chemical composition. Current NP therapeutic strategies are based on multifunctional properties, focused on combining 23 both therapeutic and imaging agents within the same particle. For example, gold NPs (Au-NP) have two major advantages in this context; they are not only able to undergo oxidation but very efficiently, transform electromagnetic energy (visible/NIR) into thermal energy. Furthermore, is very stable and the human body is capable of tolerating an amount of grams of this material without side-effects [2.6]. More recently, the possibility of using the isotope 198-Au as raw material of Au?NP synthesis, generating a nanomaterial with radioactive properties, which can emit beta and gamma radiation to the milieu a theragnostic tool (therapy and diagnosis properties) [2.2.?2.9]. Our laboratory has reported the preparation of protein NPs from Alb and stabilized by radiation-induced crosslinking [2.10]. The potential of ionizing radiation for generating nanostructures in a simple and straightforward manner has been demonstrated. In this report is described the preparation of a core/shell Au/Alb-NPs using radiation-induced structuration methodologies and their decoration with a specific peptide and characterization