Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery

Yunzhou Fang; Mallika Vadlamudi; Yingbo Huang; Xin Guo

doi:10.1007/s11095-019-2607-6

Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery

Yunzhou Fang, Mallika Vadlamudi, Yingbo Huang, Xin Guo

Experimental and Clinical Pharmacology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery. Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. The pH-sensitivity of LPP-CAT was determined by monitoring their degradation of hydrogen peroxide (H ₂ O ₂ ) and their morphologies under transmission electron microscopy (TEM) at pH 7.4 and 5.5. The ability of LPP-CAT to protect MCF-7 cells against hydrogen peroxide was measured by MTS assay. ROS levels in EA.hy926 cells were measured after treatment with LPP-CAT. Results: LPP-CAT were successfully prepared and carried an average diameter of <300 nm and ζ -potential of about +40 mV. At pH 5.5, LPP-CAT degraded H ₂ O ₂ almost 4-fold as fast as pH 7.4 and displayed drastic morphological changes of an osmotic explosion. LPP-CAT protected MCF-7 cells from lethal level of exogenous H ₂ O ₂ and significantly lowered the ROS levels in EA.hy926 cells. A lipid with a pH-sensitive conformational switch (flipid) further enhanced the protein delivery of LPP-CAT. Conclusion: LPP represents a promising nano-system for intracellular protein delivery.

Original language	English (US)
Article number	81
Journal	Pharmaceutical research
Volume	36
Issue number	6
DOIs	https://doi.org/10.1007/s11095-019-2607-6
State	Published - Jun 1 2019

Bibliographical note

Funding Information:
This work was supported by National Institute of Health (GM107823). We thank the technical consultations from Professor Leaf Huang and associates at University of North Carolina, Chapel Hill. We thank Electron Imaging Facility at University of California, Davis for access to TEM. We thank Professor Xiaoling Li at University of the Pacific for access to UV spectrometer for kinetic analyses of catalase activities.

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

intracellular delivery
liposome
magnesium phosphate nanoparticles
protein delivery
triggered release

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10.1007/s11095-019-2607-6

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@article{d37a07b8a8fd4be082173e37e27bd509,

title = "Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery",

abstract = " Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery. Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. The pH-sensitivity of LPP-CAT was determined by monitoring their degradation of hydrogen peroxide (H 2 O 2 ) and their morphologies under transmission electron microscopy (TEM) at pH 7.4 and 5.5. The ability of LPP-CAT to protect MCF-7 cells against hydrogen peroxide was measured by MTS assay. ROS levels in EA.hy926 cells were measured after treatment with LPP-CAT. Results: LPP-CAT were successfully prepared and carried an average diameter of <300 nm and ζ -potential of about +40 mV. At pH 5.5, LPP-CAT degraded H 2 O 2 almost 4-fold as fast as pH 7.4 and displayed drastic morphological changes of an osmotic explosion. LPP-CAT protected MCF-7 cells from lethal level of exogenous H 2 O 2 and significantly lowered the ROS levels in EA.hy926 cells. A lipid with a pH-sensitive conformational switch (flipid) further enhanced the protein delivery of LPP-CAT. Conclusion: LPP represents a promising nano-system for intracellular protein delivery. ",

keywords = "intracellular delivery, liposome, magnesium phosphate nanoparticles, protein delivery, triggered release",

author = "Yunzhou Fang and Mallika Vadlamudi and Yingbo Huang and Xin Guo",

note = "Funding Information: This work was supported by National Institute of Health (GM107823). We thank the technical consultations from Professor Leaf Huang and associates at University of North Carolina, Chapel Hill. We thank Electron Imaging Facility at University of California, Davis for access to TEM. We thank Professor Xiaoling Li at University of the Pacific for access to UV spectrometer for kinetic analyses of catalase activities. Publisher Copyright: {\textcopyright} 2019, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2019",

month = jun,

day = "1",

doi = "10.1007/s11095-019-2607-6",

language = "English (US)",

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T1 - Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery

AU - Fang, Yunzhou

AU - Vadlamudi, Mallika

AU - Huang, Yingbo

AU - Guo, Xin

N1 - Funding Information: This work was supported by National Institute of Health (GM107823). We thank the technical consultations from Professor Leaf Huang and associates at University of North Carolina, Chapel Hill. We thank Electron Imaging Facility at University of California, Davis for access to TEM. We thank Professor Xiaoling Li at University of the Pacific for access to UV spectrometer for kinetic analyses of catalase activities. Publisher Copyright: © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery. Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. The pH-sensitivity of LPP-CAT was determined by monitoring their degradation of hydrogen peroxide (H 2 O 2 ) and their morphologies under transmission electron microscopy (TEM) at pH 7.4 and 5.5. The ability of LPP-CAT to protect MCF-7 cells against hydrogen peroxide was measured by MTS assay. ROS levels in EA.hy926 cells were measured after treatment with LPP-CAT. Results: LPP-CAT were successfully prepared and carried an average diameter of <300 nm and ζ -potential of about +40 mV. At pH 5.5, LPP-CAT degraded H 2 O 2 almost 4-fold as fast as pH 7.4 and displayed drastic morphological changes of an osmotic explosion. LPP-CAT protected MCF-7 cells from lethal level of exogenous H 2 O 2 and significantly lowered the ROS levels in EA.hy926 cells. A lipid with a pH-sensitive conformational switch (flipid) further enhanced the protein delivery of LPP-CAT. Conclusion: LPP represents a promising nano-system for intracellular protein delivery.

AB - Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery. Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. The pH-sensitivity of LPP-CAT was determined by monitoring their degradation of hydrogen peroxide (H 2 O 2 ) and their morphologies under transmission electron microscopy (TEM) at pH 7.4 and 5.5. The ability of LPP-CAT to protect MCF-7 cells against hydrogen peroxide was measured by MTS assay. ROS levels in EA.hy926 cells were measured after treatment with LPP-CAT. Results: LPP-CAT were successfully prepared and carried an average diameter of <300 nm and ζ -potential of about +40 mV. At pH 5.5, LPP-CAT degraded H 2 O 2 almost 4-fold as fast as pH 7.4 and displayed drastic morphological changes of an osmotic explosion. LPP-CAT protected MCF-7 cells from lethal level of exogenous H 2 O 2 and significantly lowered the ROS levels in EA.hy926 cells. A lipid with a pH-sensitive conformational switch (flipid) further enhanced the protein delivery of LPP-CAT. Conclusion: LPP represents a promising nano-system for intracellular protein delivery.

KW - intracellular delivery

KW - liposome

KW - magnesium phosphate nanoparticles

KW - protein delivery

KW - triggered release

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SN - 0724-8741

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JO - Pharmaceutical research

JF - Pharmaceutical research

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ER -

Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery

Abstract

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