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Nanoscale. 2019 Jan 23;11(4):1636-1646. doi: 10.1039/c8nr07730d.

Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth.

Author information

1
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia. max.nikitin@phystech.edu and Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia and Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia and National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia.
2
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia. max.nikitin@phystech.edu and Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
3
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia. max.nikitin@phystech.edu and Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia and National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia.
4
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia. max.nikitin@phystech.edu.
5
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
6
Prokhorov General Physics, Institute of the Russian Academy of Sciences, Moscow, Russia and National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia.
7
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia and National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia.
8
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia. max.nikitin@phystech.edu and Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia and Prokhorov General Physics, Institute of the Russian Academy of Sciences, Moscow, Russia.

Abstract

Delivery of particle-based theranostic agents via their transportation on the surfaces of red blood cells, commonly referred to as RBC-hitchhiking, has historically been developed as a promising strategy for increasing the extremely poor blood circulation lifetime, primarily, of the large-sized sub-micron agents. Here, we show for the first time that RBC-hitchhiking can be extremely efficient for nanoparticle delivery and tumor treatment even in those cases when no circulation prolongation is observed. Specifically, we demonstrate that RBC-hitchhiking of certain small 100 nm particles, unlike that of the conventional sub-micron ones, can boost the delivery of non-targeted particles to lungs up to a record high value of 120-fold (and up to 40% of the injected dose). To achieve this remarkable result, we screened sub-200 nm nanoparticles of different sizes, polymer coatings and ΞΆ-potentials and identified particles with the optimal RBC adsorption/desorption behavior. Furthermore, we demonstrated that such RBC-mediated rerouting of particles to lungs can be used to fight pulmonary metastases of aggressive melanoma B16-F1. Our findings could change the general paradigm of drug delivery for cancer treatment with RBC-hitchhiking. It is not the blood circulation lifetime that is the key factor for nanoparticle efficiency, but rather the complexation of nanoparticles with the RBC. The demonstrated technology could become a valuable tool for development of new strategies based on small nanoparticles for the treatment of aggressive and small-cell types of cancer as well as other lung diseases.

PMID:
30644955
DOI:
10.1039/c8nr07730d
[Indexed for MEDLINE]

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