標題: Synthesis of Apolipoprotein B Lipoparticles to Deliver Hydrophobic/Amphiphilic Materials
作者: Chu, Hsueh-Liang
Cheng, Tsai-Mu
Chen, Hung-Wei
Chou, Fu-Hsuan
Chang, Yu-Chuan
Lin, Hsin-Yu
Liu, Shih-Yi
Liang, Yu-Chuan
Hsu, Ming-Hua
Wu, Dian-Shyeu
Li, Hsing-Yuan
Ho, Li-Ping
Wu, Ping-Ching
Chen, Fu-Rong
Chen, Gong-Shen
Shieh, Dar-Bin
Chang, Chia-Seng
Su, Chia-Hao
Yao, Zemin
Chang, Chia-Ching
材料科學與工程學系
生物科技學系
Department of Materials Science and Engineering
Department of Biological Science and Technology
關鍵字: protein reconstitution;apolipoprotein B;low-density lipoprotein;Fourier transform infrared spectroscopy;drug delivery;solution transmission electron microscopy imaging
公開日期: 14-Aug-2013
摘要: To develop a drug delivery system (DDS), it is critical to address challenging tasks such as the delivery of hydrophobic and amphiphilic compounds, cell uptake, and the metabolic fate of the drug delivery carrier. Low-density lipoprotein (LDL) has been acknowledged as the human serum transporter of natively abundant lipoparticles such as cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo B) is the only protein contained in LDL, and possesses a binding moiety for the LDL receptor that can be internalized and degraded naturally by the cell. Therefore, synthetic/reconstituting apoB lipoparticle (rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic materials. Here, we synthesized rABL in vitro, using full-length apoB through a five-step solvent exchange method, and addressed its potential as a DDS. Our rABL exhibited good biocompatibility when evaluated with cytotoxicity and cell metabolic response assays, and was stable during storage in phosphate-buffered saline at 4 degrees C for several months. Furthermore, hydrophobic superparamagnetic iron oxide nanoparticles (SPIONPs) and the anticancer drug M4N (tetra-O-methyl nordihydroguaiaretic acid), used as an imaging enhancer and lipophilic drug model, respectively, were incorporated into the rABL, leading to the formation of SPIONPs- and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier transform infrared spectroscopy suggested that rABL has a similar composition to that of LDL, and successfully incorporated SPIONPs or M4N. SPIO@rABL presented significant hepatic contrast enhancement in T-2-weighted magnetic resonance imaging in BALB/c mice, suggesting its potential application as a medical imaging contrast agent. M4N@rABL could reduce the viability of the cancer cell line A549. Interestingly, we developed solution-phase high-resolution transmission electron microscopy to observe both LDL and SPIO@rABL in the liquid state. In summary, our LDL-based DDS, rABL, has significant potential as a novel DDS for hydrophobic and amphiphilic materials, with good cell internalization properties and metabolicity.
URI: http://dx.doi.org/10.1021/am401808e
http://hdl.handle.net/11536/22554
ISSN: 1944-8244
DOI: 10.1021/am401808e
期刊: ACS APPLIED MATERIALS & INTERFACES
Volume: 5
Issue: 15
起始頁: 7509
結束頁: 7516
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