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<p>Cancer remains a leading cause of death worldwide, and traditional chemotherapy is often limited by severe side effects and drug resistance. RNA-based therapeutics, including small interfering RNA (siRNA) and messenger RNA (mRNA), offer promising alternatives, enabling targeted gene silencing and the in situ production of therapeutic proteins. However, the clinical application of RNA-based therapeutics is hampered by delivery challenges, such as low stability and inefficient cellular uptake. Soft nanoparticles have emerged as versatile vectors to overcome these barriers. This review provides a comprehensive analysis of the most promising soft nanoparticle platforms, such as lipid systems, polymeric nanoparticles, dendrimers, protein nanoparticles, and nanohydrogels, for the delivery of RNA-based anticancer drugs, with a focus on advances published between 2020 and 2025. The compositional and structural features of nanoparticles that determine the complexation, protection, targeted delivery, and controlled release of RNA are highlighted. In addition, innovative strategies that combine different types of nanocarriers or integrate them with additional therapeutic modalities are discussed. RNA drugs based on soft nanoparticles undergoing clinical trials (June 2025) are also considered.</p>

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Soft nanoparticles as delivery agents for RNA-based anticancer therapy

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Victoriya Zhogla,
  • Viktar Abashkin,
  • Pavel Padnya,
  • Jingchao Li,
  • Mingwu Shen,
  • Ivan Stoikov,
  • Dzmitry Shcharbin,
  • Xiangyang Shi

摘要

Cancer remains a leading cause of death worldwide, and traditional chemotherapy is often limited by severe side effects and drug resistance. RNA-based therapeutics, including small interfering RNA (siRNA) and messenger RNA (mRNA), offer promising alternatives, enabling targeted gene silencing and the in situ production of therapeutic proteins. However, the clinical application of RNA-based therapeutics is hampered by delivery challenges, such as low stability and inefficient cellular uptake. Soft nanoparticles have emerged as versatile vectors to overcome these barriers. This review provides a comprehensive analysis of the most promising soft nanoparticle platforms, such as lipid systems, polymeric nanoparticles, dendrimers, protein nanoparticles, and nanohydrogels, for the delivery of RNA-based anticancer drugs, with a focus on advances published between 2020 and 2025. The compositional and structural features of nanoparticles that determine the complexation, protection, targeted delivery, and controlled release of RNA are highlighted. In addition, innovative strategies that combine different types of nanocarriers or integrate them with additional therapeutic modalities are discussed. RNA drugs based on soft nanoparticles undergoing clinical trials (June 2025) are also considered.