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 - 2013 Aug 14

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Lipoproteins
Apolipoproteins B
Iron oxides
LDL Lipoproteins
Nanoparticles
Imaging techniques
Cholesterol
Medical imaging
Magnetic resonance
Cytotoxicity
High resolution transmission electron microscopy
Drug delivery
Biocompatibility
Lipids
Fourier transform infrared spectroscopy
Apolipoproteins
Assays
Phosphates
Cells
Proteins

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

Cite this

Chu, H. L., Cheng, T. M., Chen, H. W., Chou, F. H., Chang, Y. C., Lin, H. Y., ... 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
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. / Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials. In: ACS Applied Materials and Interfaces. 2013 ; Vol. 5, No. 15. pp. 7509-7516.
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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.",
author = "Chu, {Hsueh Liang} and Cheng, {Tsai Mu} and Chen, {Hung Wei} and Chou, {Fu Hsuan} and Chang, {Yu Chuan} and Lin, {Hsin Yu} and Liu, {Shih Yi} and Liang, {Yu Chuan} and Ming-Hua Hsu and Wu, {Dian Shyeu} and Li, {Hsing Yuan} and Ho, {Li Ping} and Wu, {Ping Ching} and Chen, {Fu Rong} and Chen, {Gong Shen} and Shieh, {Dar Bin} and Chang, {Chia Seng} and Su, {Chia Hao} and Zemin Yao and Chang, {Chia Ching}",
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Chu, HL, Cheng, TM, Chen, HW, Chou, FH, Chang, YC, Lin, HY, Liu, SY, Liang, YC, Hsu, M-H, Wu, DS, Li, HY, Ho, LP, Wu, PC, Chen, FR, Chen, GS, Shieh, DB, Chang, CS, Su, CH, Yao, Z & Chang, CC 2013, 'Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials', ACS Applied Materials and Interfaces, vol. 5, no. 15, pp. 7509-7516. https://doi.org/10.1021/am401808e

Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials. / 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.

In: ACS Applied Materials and Interfaces, Vol. 5, No. 15, 14.08.2013, p. 7509-7516.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/ amphiphilic materials

AU - Chu, Hsueh Liang

AU - Cheng, Tsai Mu

AU - Chen, Hung Wei

AU - Chou, Fu Hsuan

AU - Chang, Yu Chuan

AU - Lin, Hsin Yu

AU - Liu, Shih Yi

AU - Liang, Yu Chuan

AU - Hsu, Ming-Hua

AU - Wu, Dian Shyeu

AU - Li, Hsing Yuan

AU - Ho, Li Ping

AU - Wu, Ping Ching

AU - Chen, Fu Rong

AU - Chen, Gong Shen

AU - Shieh, Dar Bin

AU - Chang, Chia Seng

AU - Su, Chia Hao

AU - Yao, Zemin

AU - Chang, Chia Ching

PY - 2013/8/14

Y1 - 2013/8/14

N2 - 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.

AB - 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.

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