Enhancement of the blood-circulation time and performance of nanomedicines via the forced clearance of erythrocytes

Maxim P. Nikitin, Ivan V. Zelepukin, Victoria O. Shipunova, Ilya L. Sokolov, Sergey M. Deyev, Petr I. Nikitin

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg−1) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of short-circulating and long-circulating nanoparticle formulations by up to 32-fold. Treatment of the animals with anti-erythrocyte antibodies significantly improved the targeting of CD4+ cells in vivo with fluorescent anti-CD4-antibody-conjugated nanoparticles, the magnetically guided delivery of ferrofluid nanoparticles to subcutaneous tumour allografts and xenografts, and the treatment of subcutaneous tumour allografts with magnetically guided liposomes loaded with doxorubicin and magnetite or with clinically approved ‘stealthy’ doxorubicin liposomes. The transient and partial blocking of the mononuclear phagocyte system may enhance the performance of a wide variety of nanoparticle drugs.

Original languageEnglish
Pages (from-to)717-731
Number of pages15
JournalNature Biomedical Engineering
Volume4
Issue number7
DOIs
Publication statusPublished - 1 Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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