Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles

Abstract

Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs.

Original language	English
Article number	102317
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	32
DOIs	https://doi.org/10.1016/j.nano.2020.102317
Publication status	Published - Feb 2021

Keywords

Endocytosis
Iron oxide magnetic nanoparticles
MRI
pH profile
pHLIP

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Molecular Medicine
Biomedical Engineering
Materials Science(all)
Pharmaceutical Science

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Pershina, A. G., Brikunova, O. Y., Demin, A. M., Abakumov, M. A., Vaneev, A. N., Naumenko, V. A., Erofeev, A. S., Gorelkin, P. V., Nizamov, T. R., Muslimov, A. R., Timin, A. S., Malkeyeva, D., Kiseleva, E., Vtorushin, S. V., Larionova, I. V., Gereng, E. A., Minin, A. S., Murzakaev, A. M., Krasnov, V. P., ... Ogorodova, L. M. (2021). Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine, 32, [102317]. https://doi.org/10.1016/j.nano.2020.102317

Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles. / Pershina, Alexandra G.; Brikunova, Olga Ya; Demin, Alexander M.; Abakumov, Maxim A.; Vaneev, Alexander N.; Naumenko, Victor A.; Erofeev, Alexander S.; Gorelkin, Peter V.; Nizamov, Timur R.; Muslimov, Albert R.; Timin, Alexander S.; Malkeyeva, Dina; Kiseleva, Elena; Vtorushin, Sergey V.; Larionova, Irina V.; Gereng, Elena A.; Minin, Artem S.; Murzakaev, Aidar M.; Krasnov, Victor P.; Majouga, Alexander G.; Ogorodova, Ludmila M.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 32, 102317, 02.2021.

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

Pershina, AG, Brikunova, OY, Demin, AM, Abakumov, MA, Vaneev, AN, Naumenko, VA, Erofeev, AS, Gorelkin, PV, Nizamov, TR, Muslimov, AR, Timin, AS, Malkeyeva, D, Kiseleva, E, Vtorushin, SV, Larionova, IV, Gereng, EA, Minin, AS, Murzakaev, AM, Krasnov, VP, Majouga, AG & Ogorodova, LM 2021, 'Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 32, 102317. https://doi.org/10.1016/j.nano.2020.102317

Pershina, Alexandra G. ; Brikunova, Olga Ya ; Demin, Alexander M. ; Abakumov, Maxim A. ; Vaneev, Alexander N. ; Naumenko, Victor A. ; Erofeev, Alexander S. ; Gorelkin, Peter V. ; Nizamov, Timur R. ; Muslimov, Albert R. ; Timin, Alexander S. ; Malkeyeva, Dina ; Kiseleva, Elena ; Vtorushin, Sergey V. ; Larionova, Irina V. ; Gereng, Elena A. ; Minin, Artem S. ; Murzakaev, Aidar M. ; Krasnov, Victor P. ; Majouga, Alexander G. ; Ogorodova, Ludmila M. / Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2021 ; Vol. 32.

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title = "Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles",

abstract = "Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs.",

keywords = "Endocytosis, Iron oxide magnetic nanoparticles, MRI, pH profile, pHLIP",

author = "Pershina, {Alexandra G.} and Brikunova, {Olga Ya} and Demin, {Alexander M.} and Abakumov, {Maxim A.} and Vaneev, {Alexander N.} and Naumenko, {Victor A.} and Erofeev, {Alexander S.} and Gorelkin, {Peter V.} and Nizamov, {Timur R.} and Muslimov, {Albert R.} and Timin, {Alexander S.} and Dina Malkeyeva and Elena Kiseleva and Vtorushin, {Sergey V.} and Larionova, {Irina V.} and Gereng, {Elena A.} and Minin, {Artem S.} and Murzakaev, {Aidar M.} and Krasnov, {Victor P.} and Majouga, {Alexander G.} and Ogorodova, {Ludmila M.}",

note = "Funding Information: Funding: This work was supported by the Russian Foundation for Basic Research [grant number: 18-015-00319_a ], the Russian Science Foundation [grant number 19-79-30062 ], the Ministry of Higher Education and Science of the Russian Federation [grant number K2-2019-011 ]. Funding Information: Authors thank Eleonora Novikova for Graphical Abstract design. The experimental calculations were supported by a Tomsk Polytechnic University Competitiveness Enhancement Program grant. The MNP characterization was conducted within the framework of a state assignment (No. AAAA-A19-119011790130-3) on the equipment of the multi-access center “Spectroscopy and Analysis of Organic Compounds” at the Postovsky Institute of Organic Synthesis (UB RAS). TEM analysis was carried out at the Multiple-access Center for Microscopy of Biological Subjects, Institute of Cytology and Genetics SB RAS. The English language was corrected and certified by shevchuk-editing.com . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

doi = "10.1016/j.nano.2020.102317",

language = "English",

volume = "32",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

issn = "1549-9634",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles

AU - Pershina, Alexandra G.

AU - Brikunova, Olga Ya

AU - Demin, Alexander M.

AU - Abakumov, Maxim A.

AU - Vaneev, Alexander N.

AU - Naumenko, Victor A.

AU - Erofeev, Alexander S.

AU - Gorelkin, Peter V.

AU - Nizamov, Timur R.

AU - Muslimov, Albert R.

AU - Timin, Alexander S.

AU - Malkeyeva, Dina

AU - Kiseleva, Elena

AU - Vtorushin, Sergey V.

AU - Larionova, Irina V.

AU - Gereng, Elena A.

AU - Minin, Artem S.

AU - Murzakaev, Aidar M.

AU - Krasnov, Victor P.

AU - Majouga, Alexander G.

AU - Ogorodova, Ludmila M.

N1 - Funding Information: Funding: This work was supported by the Russian Foundation for Basic Research [grant number: 18-015-00319_a ], the Russian Science Foundation [grant number 19-79-30062 ], the Ministry of Higher Education and Science of the Russian Federation [grant number K2-2019-011 ]. Funding Information: Authors thank Eleonora Novikova for Graphical Abstract design. The experimental calculations were supported by a Tomsk Polytechnic University Competitiveness Enhancement Program grant. The MNP characterization was conducted within the framework of a state assignment (No. AAAA-A19-119011790130-3) on the equipment of the multi-access center “Spectroscopy and Analysis of Organic Compounds” at the Postovsky Institute of Organic Synthesis (UB RAS). TEM analysis was carried out at the Multiple-access Center for Microscopy of Biological Subjects, Institute of Cytology and Genetics SB RAS. The English language was corrected and certified by shevchuk-editing.com . Publisher Copyright: © 2020 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs.

AB - Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs.

KW - Endocytosis

KW - Iron oxide magnetic nanoparticles

KW - MRI

KW - pH profile

KW - pHLIP

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JO - Nanomedicine: Nanotechnology, Biology, and Medicine

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