Doctoral defence: Valeria Sidorenko "Novel anthracycline-loaded nanoparticles for precision cancer therapy"

On December 13th Valeria Sidorenko will defend her thesis "Novel anthracycline-loaded nanoparticles for precision cancer therapy". 

Supervisors: 
Visiting lecturer Lorena Simon Gracia, University of Tartu
Professor Tambet Teesalu, University of Tartu

Opponent: 
Ibane Abasolo Olaortua, Centro de Investigación Biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto De Salud Carlos III (Spain)

Summary:
Cancer treatment demands a multifaceted approach. While traditional methods like surgery and radiation therapies tackle localized tumors effectively, systemic treatments, especially chemotherapy, are crucial for combating metastatic spread. Anthracycline drugs are widely used for their broad efficacy, but their utility is limited by adverse effects like cardiotoxicity and bone marrow depression. Therefore, developing new anthracyclines with improved safety profiles is imperative. 

Another approach involves drug delivery vehicles, such as lipid and polymer particles, allowing for precise and controlled drug administration to tumor sites, thus reducing systemic toxicity. These carriers shield therapeutic agents until reaching their target, enhancing drug solubility and availability. Targeted drug delivery methods, particularly using tumor-penetrating peptides (TPPs), enhance treatment accuracy and effectiveness while minimizing side effects on healthy tissues. Such peptides selectively bind to receptors overexpressed on cancer cells, enabling precise drug delivery to tumors, thereby improving treatment outcomes. 

This doctoral thesis focuses on the preclinical development and evaluation of a novel precision cancer therapy, particularly the anthracycline prodrug Utorubicin (UTO). Two types of nanovesicles, niosomes (NSVs), and polymersomes (PS), were optimized and validated to enhance drug accumulation in tumor cells expressing specific receptors. Comprehensive in vitro and in vivo studies evaluated the cytotoxicity and treatment efficacy of TPP-targeted particles loaded with DOX or UTO. Furthermore, synergistic effects of UTO-PS with vascular-disrupting agent CA4P and TPP iRGD were investigated in treating mice with peritoneal carcinomatosis, highlighting significantly improved therapeutic outcomes and safety potential. Overall, this study demonstrates how innovative drug delivery strategies can significantly enhance cancer treatment efficacy and safety. Nanotechnology and targeted drug delivery approaches offer new avenues for developing personalized and effective cancer therapies, potentially improving patient quality of life and survival rates.