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

• Published in: Nanoscale 2019-01, Vol.11 (4), p.1636-1646
• Main Authors: Zelepukin, I. V, Yaremenko, A. V, Shipunova, V. O, Babenyshev, A. V, Balalaeva, I. V, Nikitin, P. I, Deyev, S. M, Nikitin, M. P
• Format: Article
• Language: English
• Subjects: Blood circulation; Cancer; Drug delivery systems; Erythrocytes; Lungs; Metastasis; Nanoparticles; Polymer coatings; Prolongation
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c8nr07730d

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. RBC-hitchhiking regime is shown without prolongation of nanoparticle blood circulation but with the record 120-fold boost of particle delivery to lungs. The approach is efficient for treatment of pulmonary metastases.