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Abstract <p>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 appearance of 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 (junction opener 4, 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月1日

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  • G. M. Proshkina,
  • E. I. Shramova,
  • A. B. Mirkasymov,
  • E. V. Serova,
  • S. M. Deyev

摘要

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 appearance of 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 (junction opener 4, 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.