TOXICITY ASSESSMENT OF POLYMERIC NANOPARTICLES LOADED WITH ANTITUMOR DRUGS IN CAENORHABDITIS ELEGANS

• Grant number: 25/00188-7
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: May 01, 2025
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Camila Megumi Hirokawa
• Supervisor: Prof Dr Eva Liebau
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Munster, Germany
• Associated to the scholarship: 24/00270-2 - DEVELOPMENT OF POLYMERIC NANOPARTICLES TO DELIVER CHROMOMYCIN AS A NOVEL STRATEGY FOR BREAST CANCER TREATMENT, BP.MS

Abstract

The development of novel nanotechnology-based therapies should comprise not only the complete characterization of the nanoparticles' physicochemical properties but also in vitro and in vivo activity and toxicity evaluation. Considering the well-documented toxicity of antitumor drug candidate chromomycin, studying whether nanoencapsulation modulates its toxic effects is essential. However, few efficient models are available to study nanoparticle toxicity, and most studies focus on rodents, which face several ethical challenges. Herein, we propose a toxicity assessment of polymeric nanoparticles (Pol-NPs) containing chromomycin (CA) using an alternative in vivo model: Caenorhabditis elegans (C. elegans). First introduced as an in vivo model by Brenner in the 1960s, this 1 mm-long free-living nematode displays a well-documented genetic background, short life cycle and lifespan, small size, low-cost maintenance, ease of handling and growing in the laboratory, transparent body, and presence of several organ systems, underscoring it as a robust, versatile, and well-validated model organism for in vivo studies. Initially, fluorescent-labeled and unloaded Pol-NPs will be employed to investigate the pathways of uptake and biodistribution of Pol-NPs within the C. elegans model. Toxicity assays will be performed to explore the molecular mechanisms underlying CA toxicity and assess the influence of CA encapsulation on toxicity. Finally, transgenic C. elegans reporter strains expressing GFP-tagged genes will be utilized to evaluate the stress and DNA damage response induced by CA in both its free and encapsulated forms , and analyzed by fluorescence microscopy. With this study, we expect to contribute to the development of new nanotechnology-based antitumor strategies, translation of chromomycin as a drug, and use of C. elegans as a model organism for in vivo evaluation of nanoparticles.