In vivo blockade of mononuclear phagocyte system with solid nanoparticles: Efficiency and affecting factors.

Affiliation

Mirkasymov AB(1), Zelepukin IV(2), Nikitin PI(3), Nikitin MP(4), Deyev SM(5).
Author information:
(1)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.
(2)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; National Research Nuclear University MEPhI
(Moscow Engineering Physics Institute), 115409 Moscow, Russia.
(3)National Research Nuclear University MEPhI
(Moscow Engineering Physics Institute), 115409 Moscow, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia.
(4)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia.
(5)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; National Research Nuclear University MEPhI
(Moscow Engineering Physics Institute), 115409 Moscow, Russia. Electronic address: [Email]

Abstract

Smart nanomaterials, contrast nanoparticles and drug nanocarriers of advanced targeting architecture were designed for various biomedical applications. Most of such agents demonstrate poor pharmacokinetics in vivo due to rapid elimination from the bloodstream by cells of the mononuclear phagocyte system (MPS). One of the promising methods to prolong blood circulation of the nanoparticles without their modification is MPS blockade. The method temporarily decreases macrophage endocytosis in response to uptake of a low-toxic non-functional material. The effect of different factors on the efficiency of macrophage blockade in vivo induced by solid nanomaterials has been studied here. Those include: blocker nanoparticle size, ζ-potential, surface coating, dose, mice strain, presence of tumor or inflammation. We found that the blocker particle coating type had the strongest effect on MPS blockade efficiency, which allowed to prolong functional particle blood circulation half-life 18 times. The mechanisms capable of regulation of the MPS blockade have been demonstrated, which can promote application of this phenomenon in medicine for improving delivery of diagnostic and therapeutic nanomaterials.