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

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

Abstract 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 modul...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Nanobiotechnology
Online Access:https://doi.org/10.1186/s12951-025-03542-4
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Summary:Abstract 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.
ISSN:1477-3155

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