Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents.

Abstract

To determine whether radiofrequency ablation (RFA) is more effective when combined with intratumoural injection (IT) than with intravenous injection (IV) of micelles. Balb/c mice bearing 4T1 breast cancer were used. The tumour drug accumulation and biodistribution in major organs were evaluated at different time points after IT, IV, IT+RFA and IV+RFA. Periablational drug penetration was evaluated by quantitative analysis and pathologic staining after different treatments. For long-term outcomes, mice bearing tumours were randomised into six groups (n = 7/group): the control, IV, IT, RFA alone, IV+RFA and IT+RFA groups. The end-point survival was estimated for the different treatment groups. In vivo, intratumoural drug accumulation was always much higher for IT than for IV within 48 h (p < 0.001). The IT+RFA group (3084.7 ± 985.5 μm) exhibited greater and deeper drug penetration than the IV+RFA group (686.3 ± 83.7 μm, p < 0.001). Quantitatively, the intratumoural drug accumulation in the IT+RFA group increased approximately 4.0-fold compared with that in the IV+RFA group (p < 0.001). In addition, compared with the IT treatment, the IT+RFA treatment further reduced the drug deposition in the main organs. Survival was longer in the IT+RFA group than in the IV+RFA (p = 0.033) and RF alone (p = 0.003) groups. The use of IT+RFA achieved much deeper and greater intratumoural drug penetration and accumulation, resulting in better efficacy, and decreased the systemic toxicity of nanoparticle-delivered chemotherapy. • Association of IT+RFA achieved much deeper and greater intratumoural drug penetration than of IV+RFA, leading to better therapeutic efficacy. • Compared with IV or IT chemotherapy alone, the combination with RFA decreased toxicity, especially in the IT+RFA group.