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<p>High atomic number metal-based nanoparticles (NPs) enhance radiotherapy efficacy by improving tumor multimodal imaging and intensifying radiation dosage. AGuIX-Bi represents a theranostic NP comprising gadolinium and bismuth chelates grafted on a polysiloxane core. We hypothesize that modulating the surface of AGuIX-Bi with targeted peptides will enhance the therapeutic responses of radiation therapy. The cyclic Arg-Gly-Asp (cRGD) peptide has a high affinity to RGD-binding integrins overexpressed on various tumor cells, including lung cancer. In the present study, we introduced cRGD peptides onto the surface of AGuIX-Bi NPs using a PEG spacer to form an amide bond with the free amino functions present at the surface of the NPs. In vitro, AGuIX-Bi-cRGD showed enhanced internalization of NPs via integrin binding and increased radiosensitization. In murine Lewis lung carcinoma (LLC) tumors, AGuIX-Bi-cRGD exhibited increased accumulation and retention in tumors without causing systemic toxicity. Combined with fractionated irradiation, AGuIX-Bi-cRGD converted a “cold” LLC tumor microenvironment (TME) into a “hot” one by inducing the overexpression of the immunogenic cell death marker HMGB1 and increasing the density of tumor-infiltrating CD3<sup>+</sup> CD8<sup>+</sup> cytotoxic T cells and thereby delaying tumor growth and improving mice survival. Therefore, these results suggest a potential strategy for using targeted AGuIX-Bi-cRGD NPs to sensitize lung tumors to radiation and immunotherapies.</p>

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Targeted-theranostic nanoparticles induce anti-tumor immune response in lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Zeinaf Muradova,
  • Léna Carmès,
  • Needa Brown,
  • Fabien Rossetti,
  • Romy Guthier,
  • Sayeda Yasmin-Karim,
  • Michael Lavelle,
  • Toby Morris,
  • Eder Jose Guidelli,
  • Mileni Isikawa,
  • Sandrine Dufort,
  • Guillaume Bort,
  • Olivier Tillement,
  • François Lux,
  • Ross Berbeco

摘要

High atomic number metal-based nanoparticles (NPs) enhance radiotherapy efficacy by improving tumor multimodal imaging and intensifying radiation dosage. AGuIX-Bi represents a theranostic NP comprising gadolinium and bismuth chelates grafted on a polysiloxane core. We hypothesize that modulating the surface of AGuIX-Bi with targeted peptides will enhance the therapeutic responses of radiation therapy. The cyclic Arg-Gly-Asp (cRGD) peptide has a high affinity to RGD-binding integrins overexpressed on various tumor cells, including lung cancer. In the present study, we introduced cRGD peptides onto the surface of AGuIX-Bi NPs using a PEG spacer to form an amide bond with the free amino functions present at the surface of the NPs. In vitro, AGuIX-Bi-cRGD showed enhanced internalization of NPs via integrin binding and increased radiosensitization. In murine Lewis lung carcinoma (LLC) tumors, AGuIX-Bi-cRGD exhibited increased accumulation and retention in tumors without causing systemic toxicity. Combined with fractionated irradiation, AGuIX-Bi-cRGD converted a “cold” LLC tumor microenvironment (TME) into a “hot” one by inducing the overexpression of the immunogenic cell death marker HMGB1 and increasing the density of tumor-infiltrating CD3+ CD8+ cytotoxic T cells and thereby delaying tumor growth and improving mice survival. Therefore, these results suggest a potential strategy for using targeted AGuIX-Bi-cRGD NPs to sensitize lung tumors to radiation and immunotherapies.