Improvement of Docetaxel Delivery and Tumor Radiosensitization Via Lipid Nanoparticles
Abstract
Purpose
The integration of radiosensitizing chemotherapeutics with radiotherapy represents a promising strategy to enhance tumor response. However, conventional systemic administration often results in limited tumor drug delivery, reducing radiosensitization while increasing systemic toxicity. Improving the delivery of such agents therefore presents a significant opportunity to enhance therapeutic outcomes. Lipid nanoparticles (LNPs) have emerged as a promising platform to improve chemotherapeutic delivery. Here, we investigate the use of LNPs to enhance delivery of the radiosensitizing chemotherapeutic docetaxel (DTX) to tumors and evaluate its efficacy in combination with radiotherapy.
Methods
MIA PaCa-2 (pancreatic) tumors were established in mice and used to evaluate the effects of DTX delivery on tumor response. Mice received DTX at a dose of 6 mg/kg, administered either as free DTX or lipid nanoparticle–encapsulated DTX (LNP-DTX). For combination treatment studies, tumors were irradiated 24 hours following DTX administration with a single 5 Gy dose delivered using a 6 MV linear accelerator. Tumor growth was monitored to assess treatment efficacy.
Results
In the absence of radiation, LNP-DTX resulted in a significant delay in tumor growth, whereas no comparable effect was observed with free DTX. When combined with radiotherapy, treatment with LNP-DTX led to an approximately 60% reduction in tumor volume compared to radiation alone 18 days post-treatment, demonstrating synergistic effects. In contrast, no radiosensitizing effect was observed for free DTX when combined with 5 Gy.
Conclusion
LNP delivery of DTX significantly improved therapeutic efficacy and produced synergistic radiosensitizing effects when combined with radiotherapy. Importantly, these outcomes were achieved using a de-escalated dosing regimen of DTX, highlighting the potential of this strategy to enhance treatment effectiveness while reducing drug burden, which could translate to improved patient outcomes.