Polydopamine nanoparticles as a versatile nanoplatform for antioxidant and hyperthermal therapies

Polydopamine (PDA) has emerged as a versatile biomaterial with unique properties that make it highly suitable for various biomedical applications. This thesis focuses on investigating the potential of PDA nanoparticles (PDA NPs) in antioxidant therapy and near-infrared (NIR) responsive biomedical applications. Specifically, PDA NPs were investigated as a potential therapeutic agent for mitochondrial diseases such as mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and progressive external ophthalmoplegia (PEO), as well as in the treatment of hepatocellular carcinoma (HCC). Mitochondrial diseases, specifically, are a class of rare genetic diseases characterized by dysfunctional mitochondria, where mutations in mitochondrial DNA (mtDNA) have been observed. These alterations result in the fact that the progression of these diseases, such as the studied MELAS and PEO, is characterized by high levels of oxidative stress. Herein, the ability of PDA NPs to scavenge reactive oxygen species (ROS) and protect cells against ROS-induced cellular death was investigated on MELAS and PEO patient-derived cells, stressed through a known chemical pro-oxidative stimulus. Moving forward, the focus shifted to the treatment of liver cancer, a significant global health concern, which necessitates the development of novel therapeutic approaches. PDA NPs possess inherent absorbance properties in the NIR region, making them ideal candidates for mediating photothermal therapy (PTT), one of the therapeutic strategies currently gaining attention in cancer treatment research. The capabilities of PDA NPs to convert NIR light in heat were tested against HepG2 cells, used in the literature as HCC in vitro model. In our study, we specifically aimed to target mitochondria, which play a critical role in cancer development. For this purpose, we explored a completely novel approach by coating the PDA NPs with mitochondrial membranes (MM) extracted from HepG2 mitochondria to obtain MM-coated PDA NPs (MM@PDA NPs), taking advantage of the biomimicry of MM coating. The nano-formulation was characterized before and after functionalization, in order to assess the presence of the coating around the PDA NPs. PDA NPs act as a strong antioxidant agent, with a substantial reduction in ROS levels in cellular models of MELAS and PEO. These findings highlight the potential of PDA NPs as therapeutic agents for managing mitochondrial diseases. Moreover, under NIR laser irradiation, PDA NPs exhibited excellent photothermal conversion efficiency, enabling precise and localized hyperthermia-induced cancer cell death, with higher efficacy for MM-coated PDA NPs (MM@PDA NPs). The findings presented in this thesis contribute to the growing body of knowledge on PDA nanomaterials and, by harnessing the unique characteristics of PDA NPs, we can pave the way for innovative approaches to biomedical interventions, bringing us closer to effective treatments for challenging diseases and improving the quality of life for patients worldwide.