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<p>Radiotherapy is a cornerstone of cancer treatment but is limited by its lack of specificity, causing damage to both healthy and malignant tissues. pH-sensitive nanoparticles have emerged as innovative radiosensitizers, exploiting the acidic tumor microenvironment to enhance targeted drug release, increase radiation-induced reactive oxygen species (ROS), disrupt DNA repair, and modulate key cellular pathways such as STING activation, JNK inhibition, and G2/M cell cycle arrest. This review highlights recent advances in metallic, polymeric, nanogel, and hybrid pH-sensitive nanoparticles, integrating molecular mechanisms with imaging-guided strategies to improve tumor selectivity, radiosensitization efficiency, and therapeutic outcomes. While these nanoparticles show significant preclinical promise, challenges including heterogeneous tumor microenvironments, limited tissue penetration, immune modulation, systemic toxicity, and hurdles in clinical translation remain. Collectively, pH-sensitive nanoparticles represent a promising strategy for enhancing radiotherapy efficacy, and overcoming current translational barriers is critical to realizing their full therapeutic potential.</p> Graphical Abstract <p></p>

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Utilizing pH-sensitive nanoparticles in cancer radiotherapy: mechanisms and therapeutic potential

  • 期刊论文

  • 发表日期：

    2026年1月28日

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  • Yodgor Kenjayev,
  • Nigina Khalikova,
  • Ozodbek Eshqobilov,
  • Ulugbek Axmedov,
  • Alisher Babamuratov,
  • Asliddin Xursanov

摘要

Radiotherapy is a cornerstone of cancer treatment but is limited by its lack of specificity, causing damage to both healthy and malignant tissues. pH-sensitive nanoparticles have emerged as innovative radiosensitizers, exploiting the acidic tumor microenvironment to enhance targeted drug release, increase radiation-induced reactive oxygen species (ROS), disrupt DNA repair, and modulate key cellular pathways such as STING activation, JNK inhibition, and G2/M cell cycle arrest. This review highlights recent advances in metallic, polymeric, nanogel, and hybrid pH-sensitive nanoparticles, integrating molecular mechanisms with imaging-guided strategies to improve tumor selectivity, radiosensitization efficiency, and therapeutic outcomes. While these nanoparticles show significant preclinical promise, challenges including heterogeneous tumor microenvironments, limited tissue penetration, immune modulation, systemic toxicity, and hurdles in clinical translation remain. Collectively, pH-sensitive nanoparticles represent a promising strategy for enhancing radiotherapy efficacy, and overcoming current translational barriers is critical to realizing their full therapeutic potential.

Graphical Abstract