Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles.
Nanomedicine
; 32: 102317, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33096245
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 pHâ¯6.4 than at pHâ¯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.
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Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Nanopartículas de Magnetita
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Microambiente Tumoral
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Proteínas de Membrana
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Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article