The Impact of the Protein-Opener of the Desmoglein Contacts on the Accumulation of Targeted Nanoagents in HER2-Positive Solid Tumors

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Abstract

Despite significant progress in oncotherapy, oncological diseases continue to pose a serious problem for public health. The limited penetration of nanoscale therapeutic drugs into solid tumors, due to the presence of tight intercellular junctions, does not allow achieving therapeutically effective drug concentrations in distal tumor cells, which leads to the appearenceof drug resistance. In this work, to increase the accumulation of HER2-specific small gold nanoparticles (DARPin-AuNPs) in solid tumors, the use of these particles in combination with the protein-opener of desmoglein junctions JO-4 is proposed. A quantitative assessment of gold biodistribution in mice showed that co-administration of DARPin-AuNP/JO-4 in vivo increased particle accumulation in tumors by approximately 2.5-fold compared to administration of DARPin-AuNP alone.

About the authors

G. M. Proshkina

M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: gmb@ibch.ru
Moscow, Russian Federation

E. I. Shramova

M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry RAS; Moscow Institute of Engineering Physics, National Research Nuclear University “MEPhI”

Moscow, Russian Federation; Moscow, Russian Federation

A. B. Mirkasymov

M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry RAS; Moscow Institute of Engineering Physics, National Research Nuclear University “MEPhI”

Moscow, Russian Federation; Moscow, Russian Federation

E. V. Serova

M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry RAS

Moscow, Russian Federation

S. M. Deyev

M.M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry RAS; Moscow Institute of Engineering Physics, National Research Nuclear University “MEPhI”; Ogarev National Research Mordovian State University

Moscow, Russian Federation; Moscow, Russian Federation; Saransk, Russian Federation

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