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DEVELOPMENT OF NANOPARTICLES FOR ENCAPSULATION AND DELIVERY OF CHEMOTHERAPY IN THE TREATMENT OF PULMONARY CARCINOMA

Grant number: 22/13238-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2023
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Valtencir Zucolotto
Grantee:Mariane Ansoni Ferreira
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Cancer is among the main causes of mortality and morbidity worldwide and among all neoplasms, lung cancer is the most incident type and causes the highest number of deaths worldwide. In Brazil, it is the second most common in men and women (behind only non-melanoma skin cancer). Chemotherapy remains a dominant treatment modality for many cancers at different stages. Paclitaxel (PTX) is one of the most used chemotherapy drugs in the treatment of lung tumors. However, like other drugs of the same class, PTX has some limitations, mainly in relation to the side effects caused by cell damage to normal cells, making it necessary to explore alternatives that can optimize this type of treatment. One of the innovative tools to improve the anticancer activity of chemotherapeutics is the use of a controlled release system. These systems are able to reduce side effects, increase efficacy, solubility in an aqueous environment, selectivity and safety of these drugs. Among the possible systems, there are solid lipid nanoparticles (NLS), which are nanocarriers composed of solid lipids. In addition to chemotherapy, Photodynamic Therapy (PDT) is also considered an effective treatment modality for various neoplasms and malignant tumors. In PDT, the combination and interaction of light at a specific wavelength, photosensitizer (FS) and molecular oxygen (O2) generates oxidative products that induce cell death in the target tissue. 5-aminolevulinic acid (5-ALA) is a potent fluorescent FS, a natural intermediate of the heme biosynthetic pathway and used as a precursor of protoporphyrin IX (PpIX) widely used in PDT. The combination of both therapies, TDF and chemotherapy, in a single controlled release system, can promote a synergistic effect against lung cancer, with a decrease in side effects, and an increase in efficacy resulting in optimization of treatments. Thus, this project aims to develop a system composed of NLS to encapsulate PTX and the photosensitizer 5-ALA in order to promote a more targeted and effective effect of both treatments, aiming at the synergistic effect. It is expected that the incorporation of these actives in a delivery system will improve its stability and optimize its action on cancer cells, so that the results can contribute to research and studies of treatments against this type of cancer.

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