MSc.Thesis Defense:Jalal Karimzadeh Khoei

EVELOPMENT OF NANOSCALE SYSTEMS FOR THERAPEUTIC APPLICATIONS

Jalal Karimzadeh Khoei

Materials Science and Nanoengineering, MSc. Thesis, 2024

Thesis Jury

Prof. Dr. Gözde İnce (Thesis Advisor)

Assoc. Prof. Özlem Kutlu

Prof. Dr. Mehmet Burçin Ünlü

Date & Time: July 17th, 2024 –  13:30

Place: FENS L029

Zoom Link: https://sabanciuniv.zoom.us/j/98907242749

Keywords : Nanomedicine, Nano-scale Systems, Electrospinning, Biodegradable Polymers, Photodynamic Therapy, Photothermal Therapy

Abstract

Multi-scaled nanostructured systems play a critical role in advancing therapeutic strategies. This thesis explores two separate nanostructured systems to address a few of the critical challenges implantable biomaterials face. The first part focuses on the controlled degradation of implantable patches as delivery nanocarriers for therapeutic applications. Electrospun nanofiber patches based on poly(lactic-co-glycolic acid) (PLGA) offer a promising platform for controlled drug delivery due to their biocompatibility, biodegradability, and high surface area-to-volume ratio. However, the rapid degradation of PLGA can compromise their structural integrity and efficacy over time. In this study, electrospun PLGA nanofiber patches were fabricated and then modified using initiated chemical vapor deposition (iCVD) with a copolymer of 4-vinylpyridine (4VP) and methacrylic anhydride (MAH). The p(4VP-co-MAH) thin film coating provides chemical stability against hydrolytic degradation of the PLGA nanofibers and a slight pH response. While pristine PLGA nanofiber patches exhibited a degradation rate of 33.67% and 31.91%, the presence of p(4VP-co-MAH) coating demonstrated a reduced degradation rate of 23.95% and 20.67% at pH 5.5 and pH 7.5, respectively, over 15 days. These findings suggest that the combination of PLGA nanofibers with a p(4VP-co-MAH) copolymer coating represents a promising approach for creating robust and efficient delivery platforms. In the second part, we developed multifunctional nanoparticles for combined Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) to potentially improve cancer treatment. This study focuses on the development of a coreshell nanoparticle including Rose Bengal (RB)-modified Barium Titanate (BT) as the core and Polydopamine (PDA) as the shell (BTRB@PDA) using Layer-by-Layer assembly (LbL) and dipcoating strategies for dual PDT/PTT. The Second Harmonic Generation (SHG) property of the BT facilitated the conversion of tissue-penetrating laser to visible light, activating the RB to generate Reactive Oxygen Species (ROS). Our findings showed that the developed BTRB@PDA has ROS generation using a chemical indicator, which underwent a 13% and 6% absorbance peak decrease in UV-Vis for 300 and 100 ug/ml, respectively. Also, the photothermal activity led to the heat generation up to 45 °C using 1030 fs and 808 nm lasers, respectively. This shows the suitability of BTRB@PDA as a platform for PDT/PTT and suggests promising prospects for synergistic cancer therapy.