Radionuclide-labeled gold nanoparticles for nuclei-targeting internal radio-immunity therapy

Abstract

Radionuclide therapy is an important form of tumor internal radiation therapy (IRT), but its curative effect is restricted by the low radiation intensity and poor targeting ability of nuclides, which hampers efficient killing of DNA. Moreover, the limited penetration depth and nonuniform dose distribution of rays result in “blind” regions with residual living cancer cells, which increases the risk of tumor metastasis. Herein, we developed a new strategy to tactfully incorporate IRT with immunotherapy to achieve highly efficient synergistic therapy. Specifically, gold nanoparticles (AuNPs) co-modified with radioactive iodine-131 and the twin arginine translocation (TAT) peptide (¹³¹I-AuNPs-TAT) were constructed, in which TAT-guided nuclei targeting provided highly concentrated β-rays to the most radiosensitive DNA. Meanwhile, β⁻ electrons dashed on AuNPs with a sudden drop in speed can transform into low-dosage X-ray bremsstrahlung radiation. X-rays have a longer penetration depth than β-rays and are able to induce a strong immune response, thus eliminating the area that is blind to short-range β-rays resulting from the limited dose distribution. This method, named “internal radio-immunity therapy (IRIT)”, is a unique approach that combines IRT with immunotherapy to not only enhance radiotherapeutic efficacy but also broaden the clinical applications of ¹³¹I, thereby demonstrating great potential for scientific research and clinical applications.