Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents
Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents
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瘤内胶束紫杉醇与射频消融的组合:对啮齿动物的疗效和毒性
DOI:
10.1007/s00330-019-06207-7
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发表时间:
2019-11-01
影响因子:
5.9
通讯作者:
Yang, Wei
中科院分区:
文献类型:
--
作者:
Wu, Hao;Fan, Zhi-Pu;Yang, Wei
ObjectivesTo determine whether radiofrequency ablation (RFA) is more effective when combined with intratumoural injection (IT) than with intravenous injection (IV) of micelles.Materials and methodsBalb/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.ResultsIn 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.ConclusionThe 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.Key Points• 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.