Issue 4, 2019

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

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 ζ-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.

Graphical abstract: Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth

Article information

Article type
Paper
Submitted
22 set 2018
Accepted
12 dez 2018
First published
20 dez 2018

Nanoscale, 2019,11, 1636-1646

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

I. V. Zelepukin, A. V. Yaremenko, V. O. Shipunova, A. V. Babenyshev, I. V. Balalaeva, P. I. Nikitin, S. M. Deyev and M. P. Nikitin, Nanoscale, 2019, 11, 1636 DOI: 10.1039/C8NR07730D

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