Cubosomes as nanocarriers for cancer treatment: synchrotron light techniques applied in structural and performance studies of nanoparticles in tumor cell lines and in complex biological environments

• Grant number: 22/02378-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2022
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Diego Stéfani Teodoro Martinez
• Grantee: Iris Renata Sousa Ribeiro
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Cancer is a disease with high mortality rate worldwide causing approximately 10 million of deaths in 2020 according to Instituto Nacional de Câncer (INCA). Chemotherapy is the most used method to treat this disease, but it is extremely cytotoxic. In this regard, the use of nanoparticles (NPs) incorporating drugs is promising for therapeutic purposes as it increases the effectiveness against cancer and minimizes adverse effects. Particularly, cubosomes (lipid bicontinuous cubic phase NPs) have been emerged as a powerful platform for cancer treatment due to their (i) biocompatibility and (ii) ability to encapsulate both hydrophilic and lipophilic drugs and (iii) to provide a controlled release of drugs. While these advantages are of pivotal importance toward high-performance therapeutic procedures, investigations regarding the structural variations of cubosomes throughout the drug encapsulation process and detailed analyzes of the performance of these systems in cell cultures and in complex biological environments are still lacking in the literature. Accordingly, this project seeks remarkable advances with regard to characterization of cubosomes in the absence and presence of drugs and a comprehensive understanding of their mechanism of action into different tumor cell lines, using synchrotron radiation as the main analysis tool. Measurements of time-resolved small-angle X-ray scattering (TR-SAXS, in the Sapucaia beamline in Sirius) will be performed during the process of incorporation of drugs into cubosomes, in order to determine their encapsulation kinetics. Additionally, it is proposed the use of an unprecedented methodology to determine the cytolocation of such systems, based on the use of coherent diffraction imaging (CDI, in the Cateretê beamline, also in Sirius), named Ptychography CDI (PCDI). Finally, conventional techniques will also be used to evaluate the performance of cubosomes in cell cultures and in media such as human plasma. These points play a key role for the translation of increasingly efficient nanomedicines into the clinical practice.