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

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

Результат исследований: Материалы для журналаСтатьярецензирование

Аннотация

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.

Язык оригиналаАнглийский
Номер статьи102317
ЖурналNanomedicine: Nanotechnology, Biology, and Medicine
Том32
DOI
СостояниеОпубликовано - фев 2021

ASJC Scopus subject areas

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

Fingerprint Подробные сведения о темах исследования «Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles». Вместе они формируют уникальный семантический отпечаток (fingerprint).

Цитировать