pH-triggered delivery of magnetic nanoparticles depends on tumor volume

Alexandra G Pershina; Olga Ya Brikunova; Alexander M Demin; Oleg B Shevelev; Ivan A Razumov; Evgenii L Zavjalov; Dina Malkeyeva; Elena Kiseleva; Nadezhda V Krakhmal'; Sergey V Vtorushin; Vasily L Yarnykh; Vladimir V Ivanov; Raisa I Pleshko; Victor P Krasnov; Ludmila M Ogorodova

doi:10.1016/j.nano.2019.102086

pH-triggered delivery of magnetic nanoparticles depends on tumor volume

Nanomedicine. 2020 Jan:23:102086. doi: 10.1016/j.nano.2019.102086. Epub 2019 Aug 23.

Authors

Affiliations

¹ Siberian State Medical University, Tomsk, Russia; National Research Tomsk Polytechnic University, Tomsk, Russia. Electronic address: allysyz@mail.ru.
² Siberian State Medical University, Tomsk, Russia; National Research Tomsk Polytechnic University, Tomsk, Russia.
³ Postovsky Institute of Organic Synthesis UB RAS, Yekaterinburg, Russia.
⁴ Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.
⁵ Siberian State Medical University, Tomsk, Russia.
⁶ Department of Radiology, University of Washington, WA, USA; Research Institute of Biology and Biophysics, National Research Tomsk State University, Tomsk, Russia.

PMID: 31449887
DOI: 10.1016/j.nano.2019.102086

Abstract

Nowadays there is growing recognition of the fact that biological systems have a greater impact on nanoparticle target delivery in tumors than nanoparticle design. Here we investigate the targeted delivery of Fe₃O₄ magnetic nanoparticles conjugated with pH-low-insertion peptide (MNP-pHLIP) on orthotopically induced MDA-MB-231 human breast carcinoma xenografts of varying volumes as a model of cancer progression. Using in vivo magnetic resonance imaging and subsequent determination of iron content in tumor samples by inductively coupled plasma atomic emission spectroscopy we found that MNP-pHLIP accumulation depends on tumor volume. Transmission electron microscopy, histological analysis and immunohistochemical staining of tumor samples suggest that blood vessel distribution is the key factor in determining the success of the accumulation of nanoparticles in tumors.

Keywords: Iron oxide magnetic nanoparticle; MRI; Targeting; Tumor; pHLIP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Delayed-Action Preparations / chemistry
Delayed-Action Preparations / pharmacology
Female
Humans
Hydrogen-Ion Concentration
Magnetite Nanoparticles* / chemistry
Magnetite Nanoparticles* / therapeutic use
Mice
Mice, SCID
Xenograft Model Antitumor Assays

Substances

Delayed-Action Preparations
Magnetite Nanoparticles