Dual Responsive Metal-cross-linking Polymeric Nanoshell to Perturb the Intracellular Redox Balance for Combined Chemo, Chemodynamic and photothermal Therapy

• Main Authors: Lin, Yu-Feng, 林裕峰
• Other Authors: Huang, Yu-Fen
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/epa78g

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 107 === Development of nanomaterials with stimuli-responsive and multiple therapeutic modalities has gradually become a promising strategy for cancer treatment. Herein, the coordination-based metal-crosslinking polymeric nanoshell (MPNS) was introduced for the design of a glutathione (GSH) and photothermal dual responsive drug delivery system for combine chemo therapy (CT) / chemodynamic therapy (CDT) / photothermal therapy (PTT) therapy. In MPNS, ferric ion plays a crucial role to connect polydopamine (PDA) and polyacrylic acid (PAA) and makes the structure stable in the physiologic conditions. The chemo drug doxorubicin (Dox) was selected as a model drug which having some metal ion binding domain and an aromatic rich structure. Dox was successfully loading on to the drug carrier with high payload and forming the MPNSD through metal chelating and π-π interaction. Owing to the overproduction of glutathione in the tumor cells, Dox was released through the extraction and reduction of ferric ion by endogenous GSH. Enhanced reactive oxygen species (ROS) produced via ferrous-ion mediated Fenton reaction is associated with the chemo effect induced by Dox, leading tumor cell to an efficient apoptotic cell death. Additionally, in response to NIR laser irradiation, the photo induce hyperthermia can also damage the tumor cells and enhances the release of Dox to accelerating more cell death. The combination of CT/CDT/PTT therapy strategy exhibited an additive effect that allows an improved cancer-treatment than chemotherapy or photothermal therapy alone. Overall, MPNS showing the ability to generate ROS, providing a new avenue for therapeutic improvement in combination with other anticancer treatments.