PH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery

Hong Jae Lee; Da Eun Kim; Dong Jin Park; Gi Hyun Choi; Dal Nim Yang; Jung Sun Heo; Sang Cheon Lee

doi:10.1016/j.colsurfb.2016.05.039

PH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery

Hong Jae Lee, Da Eun Kim, Dong Jin Park, Gi Hyun Choi, Dal Nim Yang, Jung Sun Heo, Sang Cheon Lee

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

60 Citations (Scopus)

Abstract

We describe a calcium carbonate (CaCO₃) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO₃-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO₃ core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO₃ core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Colloids and Surfaces B: Biointerfaces
Volume	146
DOIs	https://doi.org/10.1016/j.colsurfb.2016.05.039
Publication status	Published - 1 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.

Keywords

Calcium carbonate
Intracellular delivery
Mineralization
Nanocarrier
Nitric oxide

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10.1016/j.colsurfb.2016.05.039

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title = "PH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery",

abstract = "We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).",

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AU - Lee, Hong Jae

AU - Kim, Da Eun

AU - Park, Dong Jin

AU - Choi, Gi Hyun

AU - Yang, Dal Nim

AU - Heo, Jung Sun

AU - Lee, Sang Cheon

PY - 2016/10/1

Y1 - 2016/10/1

N2 - We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).

AB - We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).

KW - Calcium carbonate

KW - Intracellular delivery

KW - Mineralization

KW - Nanocarrier

KW - Nitric oxide

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SN - 0927-7765

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JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

ER -

PH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery

Abstract

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Keywords

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