Radiosensitization by Docetaxel Prodrug-Loaded Lipid Nanoparticles in Pancreatic Cancer Xenografts

Cancer treatments are limited by poor tumor specificity and toxicity. We tested a radiosensitizing approach using PEG/RGD-functionalized gold nanoparticles (GNPs), a lipid-nanoparticle-encapsulated docetaxel prodrug (LNP_DTX-P), and external-beam radiotherapy (RT). In MIA PaCa-2 xenografts, intravenous GNPs (2 mg/kg) and LNP_DTX-P (6 mg/kg) were given before 5 Gy RT. Both LNP_DTX-P + RT and GNPs + LNP_DTX-P + RT reduced tumor volume by ~40% and significantly prolonged survival versus RT alone (p < 0.001). Adding GNPs did not enhance efficacy, indicating LNP_DTX-P was the main driver under this regimen. These results demonstrate nanocarrier-enabled radiosensitization in vivo and support further studies toward clinical translation.