| Summary: | 博士 === 國立臺灣大學 === 醫學工程學研究所 === 106 === The development of multiple functional nanoparticles can be applied in engineering, materials, the environment and medical fields. In particular, nanomedicine has attracted many researchers focusing on cancer treatment. Versatile nanocarriers are given different functional roles depending on the properties of the materials. Commonly used multi-functional nanocarriers mainly include liposomes, micelles, dendrimers, gold nanoparticles, carbon nanotubes, and proteins. Protein carriers have the advantages of high stability, high biocompatibility, biodegradability, low cytotoxicity, and low immunogenicity. Therefore, protein carriers are valuable carriers for further applications in humans.
This dissertation is separated into two parts with the principal research focusing on a drug carrier based on an apoferritin nanocage for cancer diagnosis or treatment. The first part is apoferritin (AF) encapsulated with oxaliplatin and conjugated with panitumumab for the treatment of colorectal cancer. Oxaliplatin and panitumumab have been used as a first-line therapy for metastasis in the treatment of colorectal cancer. Panitumumab has the capability to recognize a tumor cell surface marker called epidermal growth factor receptor (EGFR) and can accurately kill tumor cells and reduce side effects. When protein nanocarriers were targeted the cell surface marker, AF was internalized into the endosome and lysosome through receptor-mediated endocytosis. Then, AF was disassembled into subunits, and the containing drugs were released into acidic environments. The results showed that the oxaliplatin-loaded AF conjugated with panitumumab (AFPO) could inhibit tumor growth and reduce side effects.
The second part of the research examines the therapeutic efficacy of a nanocage loaded with a chemotherapy drug and photosensitizer. Apoferritin nanocages were loaded with doxorubicin (AF-DOX NCs), and the ADS-780 molecules were assembled on the surface of AF-DOX NCs to form a homogenously self-assembled structure, called “apoferritin loaded with doxorubicin (DOX) and ADS-780 near-infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs).” The ADNIR NPs were disrupted into AF-DOX NCs and increased the release of doxorubicin, which enhanced the cytotoxicity. Then, the photothermal theranostics was evaluated by injecting the ADNIR NPs into tumor-bearing mice and then exposing them to an NIR laser light after the nanoparticles substantially accumulated in the tumor site in 24 h. The results showed that the tumor growth was efficiently inhibited under the NIR light irradiation region, and the normal tissue had no obvious damage.
In summary, we hope to establish a platform based on an apoferritin nanocage. It has a unique structure, wherein the inner cavity could be loaded with small molecules, and the outer surface could be modified with antibody- or peptide-targeting ligands for chemotherapy. Furthermore, the photosensitizer could also be loaded with nanocages for cancer diagnosis and photothermal therapy.
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