Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials

Hsueh Liang Chu, Tsai Mu Cheng, Hung Wei Chen, Fu Hsuan Chou, Yu Chuan Chang, Hsin Yu Lin, Shih Yi Liu, Yu Chuan Liang, Ming Hua Hsu, Dian Shyeu Wu, Hsing Yuan Li, Li Ping Ho, Ping Ching Wu, Fu Rong Chen, Gong Shen Chen, Dar Bin Shieh, Chia Seng Chang, Chia Hao Su, Zemin Yao, Chia Ching Chang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)7509-7516
Number of pages8
JournalACS Applied Materials and Interfaces
Volume5
Issue number15
DOIs
Publication statusPublished - Aug 14 2013

Keywords

  • apolipoprotein B
  • drug delivery
  • Fourier transform infrared spectroscopy
  • low-density lipoprotein
  • protein reconstitution
  • solution transmission electron microscopy imaging

ASJC Scopus subject areas

  • Materials Science(all)
  • Medicine(all)

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  • Cite this

    Chu, H. L., Cheng, T. M., Chen, H. W., Chou, F. H., Chang, Y. C., Lin, H. Y., Liu, S. Y., Liang, Y. C., Hsu, M. H., Wu, D. S., Li, H. Y., Ho, L. P., Wu, P. C., Chen, F. R., Chen, G. S., Shieh, D. B., Chang, C. S., Su, C. H., Yao, Z., & Chang, C. C. (2013). Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials. ACS Applied Materials and Interfaces, 5(15), 7509-7516. https://doi.org/10.1021/am401808e