Bioactive Antiangiogenic Lipid Nanoparticles for Inhibiting Residual Tumor Growth after Insufficient Radiofrequency Ablation

Radiofrequency ablation (RFA) is a safe and minimally invasive procedure and had been recommended as the first-line treatment for early stage hepatocellular carcinoma (HCC) by NCCN and CSCO guideline. However, it had been reported that insufficient radiofrequency ablation (IRFA) was the main cause of recurrence and metastasis for patients who underwent RFA. Angiogenesis in residual tumor after IRFA was one of the main reasons for tumor progression. Although a variety of antiangiogenesis drugs had been clinically applied, systemic side effects and treatment resistance may lead to poor prognosis. Herein, we constructed a bioactive lipid nanoparticle, on the basis of dipalmitoyl phosphatidic acid (DPPA LPs), to inhibit the growth of residual tumor via antiangiogenesis. We illustrated that angiogenetic factors (VEGFA and CUX1/FGF1 axis) were significantly upregulated in residual tumor after IRFA. DPPA LPs could significantly downregulate the expression of CUX1, FGF1, and VEGFA on tumor cells in both in vitro and in vivo experiments. While the residual tumor growth after IRFA was reduced through inhibition of neovascularization, which led to prolonged survival of tumor-bearing mice. Besides, DPPA LPs showed no significant in vivo toxicity for main organs. Thus, antiangiogenic DPPA LPs could be a robust, safe, and effective platform as a promising therapeutic modality for residual tumor after IRFA.