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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U2 - 10.1016/j.nano.2020.102317
DO - 10.1016/j.nano.2020.102317
M3 - Article
C2 - 33096245
AN - SCOPUS:85096206023
VL - 32
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
M1 - 102317
ER -