Lipid-based nanocarriers in antineoplastic chemotherapy: from experimental design and functionalization to in vivo testing, with the goal of enhancing efficacy and reducing the toxicity of breast cancer treatment

• Grant number: 24/02479-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Eneida de Paula
• Grantee: Eneida de Paula
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Gustavo Henrique Rodrigues da Silva ; Hery Mitsutake ; Iola Melissa Fernandes Duarte ; Juliana Damasceno Oliveira ; Lucimara Gaziola de la Torre ; Ludmilla David de Moura ; Márcia Cristina Breitkreitz ; Thelma de Aguiar Pertinhez
• Associated scholarship(s): 25/01405-1 - In vitro cytotoxicity of lipid nanoparticles functionalized with cannabinoid compounds for encapsulation of the chemotherapy drug paclitaxel, BP.IC

Abstract

Breast cancer is a huge public health problem and the second most important cause of cancer deaths among women, in Brazil. Relapse and metastasis are observed in up to 30% of patients after conventional treatment and may cause death. Furthermore, conventional therapies themselves often contribute to numerous adverse effects. The development of drug delivery systems (DDS) can reduce such undesirable effects of canonical antineoplastics and/or target them to the tumor. In this project we intend to develop and to characterize lipid-based nanoformulations (such as liposomes and nanostructured lipid carriers) for the treatment of breast cancer. Nanostructured lipid carriers (NLC) are good drug delivery platforms that may be functionalized with natural excipients of intrinsic pharmacological activities or targeting molecules that direct them to the tumor cells. Besides the incorporation of functional excipients - such as essential oils or signal molecules (GE11 peptide) - we also intend to combine therapeutic agents to enhance the efficacy of antitumor treatments by the DDS. Design of Experiments will be employed for the development of the nanoformulations that will be characterized by different techniques (DLS, NTA, Raman imaging, electron microscopy, &) and regarding release kinetics and shelf-stability. The cytotoxicity of such DDS will be evaluated to access their internalization/effect in tumor cells from murine and human breast adenocarcinoma (eg 4T1-luc and MCF-7 lineages, respectively) and normal (NIH/3T3) cells. Preclinical models of orthotopically induced breast adenocarcinoma will be employed to evaluate the treatments with DDS, taking into consideration hematological, biochemical, and morphological parameters. We hope to produce innovative and effective nanotechnological platforms (more potent, with lower side-effects and metastasis rates) and that can improve the life-quality of breast cancer patients. (AU)