Nanostructured radiation-induced protein based systems as carriers for chemoterapeuticals

• Grant number: 15/13979-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): November 01, 2015
• Effective date (End): October 31, 2017
• Field of knowledge: Engineering - Materials and Metallurgical Engineering
• Principal Investigator: Ademar Benévolo Lugão
• Grantee: Gustavo Henrique Costa Varca
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Nanotechnology has broadened the options for delivery of agents of biotechnological and clinical relevance. Regarding antitumor/cancer drugs lots of attention has been driven nowadays towards taxanes formulation using protein particles at nano/sub-micron level. Paclitaxel and albumin complexes are theme of constant research and received final approval for commercialization this decade. In this work we aim to synthesize and evaluate protein nanoparticles, by means of albumin for parenteral use and papain for topical applications, by the use of ionizing irradiation, in absence of toxic monomers of solvents, as an attempt to overcome limitations of available protein-based nanocarriers, as novel option for the administration of chemotherapic agents or radiopharmaceuticals, with reduced toxicity and low cost. For this purpose, the proteins will be irradiated in a gammacell irradiator in presence of solvents. This nanocarriers will be evaluated according to their morphological properties using transmission electron microscopy, and particle size by Dynamic light scattering. The mechanism of nanoparticle formation will be determined by means of computational, pulse-radiolysis and mass spectrometry studies, and, the nanotoxicity/biocompatibility, considering cell toxicity, mechanism of cell death, nanoparticle-cell interaction, inflammatory and immunogenic potential. After careful evaluation, paclitaxel loading will be performed and quantification and encapsulation efficiency will also be determined.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

QUEIROZ, R. G.; VARCA, G. H. C.; KADLUBOWSKI, S.; ULANSKI, P.; LUGAO, A. B.. Radiation-synthesized protein-based drug carriers: Size-controlled BSA nanoparticles. International Journal of Biological Macromolecules, v. 85, p. 82-91, APR 2016. (15/13979-0)

GONCALVES, LIVIA DE SOUZA; FRANCHI, MARIANA; MATHOR, MONICA B.; LUGAO, ADEMAR B.; CARVALHO, VICTOR H.; MEDEIROS, MARISA H. G.; ARTIOLI, GUILHERME GIANNINI; VARCA, GUSTAVO H. C.. The molecular structure of beta-alanine is resistant to sterilising doses of gamma radiation. PLoS One, v. 14, n. 1, JAN 15 2019. (14/11948-8, 13/07937-8, 15/13979-0, 15/22686-7)