Fabrication of NIR-iron oxide core@photosensitizer drug nanogold-polymer carriers for a combination of photothermal-photodynamic therapy and magnetic resonance enhancement.

• Main Authors: Yan-Liang Lin, 林彥良
• Other Authors: Yu-Te Wu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/85322517587883976678

碩士 === 國立陽明大學 === 生醫光電研究所 === 103 === The combination of therapeutic and diagnostic treatments has become a new notion in the war with various deadly diseases such as malignancies. Here, we designed a multifunctional nanoparticles, which is followed with self-assembly of bifunctional poly(styrene-alt-maleic acid) (PSMA) and metal ions to build up metal oxide-polymer core-shell structure. After spontaneous redox reaction between polymer and HAuCl4, the Au nanoparticles were anchor to the surface of metal oxide-polymer core-shell nanoparticles. In the second works, methylene blue (MB), a known effective photosensitizer (PS), was utilized to combine with Fe3O4@PSMA@Au nanoparticles (NPs) via an intermolecular interaction between the negatively charged polymer layer and positively charged MB. The obtained MB-Fe3O4@PSMA@Au nanocomposites (NPs) are not only be used as Magnetic Resonance Imaging(MRI) whole-body with high contrast for diagnosis, but also can generate cytotoxic singlet oxygen under 660nm light excitation for photodynamic therapy(PDT), as well as rapidly and efficiently convert the 1064 nm laser energy into thermal energy for photothermal therapy (PTT). In addition, we demonstrated the potential imaging abilities with T2-lowing effect (over 200 mM-1s-1) for MRI contrast agent. In terms of photodynamic therapy (PDT), the MB-Fe3O4@PSMA@Au NPs produced a high quantum yield of singlet oxygen molecules, over 26% as much as that of MB-Fe3O4@PSMA NPs, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. A remarkably improved and synergistic therapeutic effect compared to PTT or PDT alone is obtained, providing lower power and high therapeutic efficiency for cancer treatment. In addition, after FA-PEG modification on the PSMA surface to enhance malignant cells selectivity and after TPP-PEG modification on the PSMA surface to change the position of drug release, MB was loaded on to the PSMA layer of biocompatible Fe3O4@PSMA@Au NPs. In the combinatorial PDT/PTT effect, FA(TPP)-MB-Fe3O4@PSMA@Au NPs had better than MB-Fe3O4@PSMA@Au NPs. Therefore, benefiting from the Simple synthetic method, FA(TPP)-MB-Fe3O4@PSMA@Au NPs developed herein are promising as an integrated theranostic probe for MRI image-guided combinatorial PDT/PTT of cancer.