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

  • Yunzhou Fang
  • Mallika Vadlamudi
  • Yingbo Huang
  • Xin GuoEmail author
Research Paper



To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery.


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 (H2O2) 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.


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 H2O2 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 H2O2 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.


LPP represents a promising nano-system for intracellular protein delivery.


intracellular delivery liposome magnesium phosphate nanoparticles protein delivery triggered release 





HEPES buffered saline (10 mM HEPES, 150 mM NaCl, pH 7.4)


Cationic liposomes loaded with catalase


L – CAT containing flipid in the lipid membrane


Lipid-coated magnesium phosphate nanoparticles


Lipid-coated magnesium phosphate nanoparticles loaded with catalase


LPP – CAT containing flipid in the lipid membrane


Magnesium phosphate nanoparticles


Reactive oxygen species

Flipid (F)

Bisdodecyl-4-hydroxy-trans-5-morpholinocyclohexane-trans-1,2-dicarboxylate, a lipidic amphiphile containing a pH-sensitive conformational switch


Transmission electron microscopy


Acknowledgments and Disclosures

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.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health SciencesUniversity of the PacificStocktonUSA

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