MSc. Thesis Defense: Buğra Şenel
Investigation of Therapeutic Effects of Targeted Polymeric Drug Delivery System in Breast Cancer
Buğra Şenel
Molecular Biology, Genetics and Bioengineering, MSc. Thesis, 2025
Thesis Jury
Assoc. Prof. Dr. Özlem Kutlu (Thesis Advisor)
Prof. Dr. Gözde İnce (Thesis co-Advisor)
Assoc. Prof. Dr. Feray Bakan Mısırlıoğlu
Asst. Prof. Dr. Stuart James Lucas
Prof. Dr. Mehmet Burçin Ünlü
Date & Time: July 17th, 2025 – 12:40 PM
Place: FMAN G041
Zoom Link: https://sabanciuniv.zoom.us/j/
Meeting ID: 986 0650 2017
Keywords: Breast cancer, Drug delivery system, Nanomedicine, Chemotherapy, Photothermal therapy, Photodynamic therapy
Abstract
Nanomedicine has emerged as a transformative treatment approach in cancer therapeutics. The limitations of conventional treatments were addressed by enabling the targeted delivery of therapeutic agents directly to tumor sites. This strategy enhances efficacy while minimizing systemic toxicity. By designing multifunctional nanoparticles, it is possible to combine therapeutic modalities into a single, nanoparticle drug platform. This thesis investigated the therapeutic efficacy of a multifunctional drug delivery system for breast cancer. A core-shell nanoparticle was synthesized with a Barium Titanate-Rose Bengal (BTRB) core for Near-Infrared (NIR) light-triggered photodynamic therapy (PDT) and a Polydopamine (PDA) shell for photothermal therapy (PTT). To achieve active targeting of distinct breast cancer subtypes, the outer layer surface of nanoparticles was dually functionalized with Trastuzumab (TRZ) and Estradiol (EST) to target HER2-positive and Estrogen Receptor (ER) positive cells, respectively. Furthermore, that multifunctional TRZ-EST/BTRB@PDA nanoparticles were incorporated into an electrospun patch to evaluate their potential for localized, implantable drug delivery. In this study, in vitro studies were conducted on HER2-positive (SKBR3) and ER-positive (MCF7) breast cancer cell lines, with a non-cancerous breast epithelial cell line (MCF12A) as a control. The results demonstrated that the functionalized nanoparticles exhibited significantly higher cellular uptake by cancer cells. Laser activation for PTT (808 nm) and PDT (1030 nm) led to considerable cancer cell death, which was linked to a significant increase in heat production, intracellular Reactive Oxygen Species (ROS) production and the induction of apoptosis.. Additionally, it was demonstrated that the nanoparticle system successfully induced G1 phase cell cycle arrest in HER2-positive cancer cells. The nanoparticle-loaded patch also showed successful release and targeted cytotoxicity. As a result, this nanoparticle drug delivery system establishes a multifunctional nanoplatform that effectively combines targeted chemotherapy with dual phototherapies. The in vitro data highlights the potential of this system for developing more effective and alternative targeted breast cancer treatments.