Development of Albumin Coated Iron Oxide Nanoparticles as Drug Delivery Vehicles in Photodynamic Therapy

• Main Authors: Hu, Chun-Yu, 胡淳育
• Other Authors: Huang, Yu-Fen
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/78277846454579237764

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 103 === Photodynamic therapy (PDT) requires combination of a photosensitizer (PS), light and oxygen; it is a non-invasive therapeutic modality which is widely used in cancer clinical trial. Most existing PSs are hydrophobic in nature. PDT’s oxidative damage is significantly reduced by the low efficiency of reactive oxygen species (ROS) production. Owing to the high binding affinity of serum albumin toward Protoporphyrin IX (PpIX), bovine serum albumin (BSA) was applied as a carrier for PDT drug in the current study.The high aqueous solubility of BSA makes it an ideal candidate to stabilize hydrophobic porous hollow Fe3O4 nanoparticles (PHNPs). This process is done through one step oil-in-water emulsion under optimal ultrasonication condition. The morphology and particle size of the BSA:PpIX:PHNPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The resultant nanocluster demonstrated a narrow size distribution with a mean hydrodynamic diameter of 152.9 ± 29.0 nm. Spectroscopic measurement confirmed high PpIX-loading efficiency, which was biocompatible and stable in various buffers. Furthermore, in vitro cytotoxicity of BSA:PpIX:PHNPs was tested in Tramp C1 cells via MTT assay and significant improvement in therapeutic efficacy was achieved with 30 min-red laser (632 nm) irradiation. This result was also consistent with an increase of ROS generation in cancer cells and was demonstrated using flow cytometry. In addition, BSA:PpIX:PHNPs exhibit high transverse relaxivity in MRI as the contrast agents (CAs).PEGylated nanoparticles have been proposed as enabling evasion by RAW 264.7 cells and reducing blood plasma protein adsorption. In this work, methoxy PEG succinimidyl carboxymethyl ester was covalently attached to BSA and followed by NHS ester-amine reaction in phosphate buffer (pH 8). PEG-BSA and hydrophobic porous hollow Fe3O4 nanoparticles (PHNPs) were stabilized through one step oil-in-water emulsion under optimal ultrasonication condition. Our results demonstrate that PEGylation of BSA:PpIX:PHNPs can modulate cellular uptake by RAW 264.7 cells.BSA:PpIX:PHNPs have shown great potential both in drug delivery and photodynamic therapy.Herein, we developed a doxorubicin (Dox)-loaded BSA:PpIX:PHNPs to facilitate combined chemotherapy and photodynamic therapy in one system. BSA:Dox:PpIX:PHNPs, show high loading efficiency of Dox and PpIX. Comparing in vitro cytotoxicity assays of BSA:Dox:PHNPs &; BSA:PpIX:PHNPs with BSA:Dox:PpIX:PHNPs, we demonstrated that BSA:Dox:PpIX:PHNPs have higher therapeutic efficacy during photodynamic therapy. The ability of BSA:Dox:PpIX:PHNPs to combine local specific chemotherapy with external photodynamic therapy significantly improves therapeutic efficacy of cancer treatment.Our findings suggest that albumin coated magnetic nanoparticles exhibit great potential as a diagnostic &; therapeutic system in cancer therapy.