Inhibition of Cancer Angiogenesis Using Triptolide Nanoparticles
Tumor-associated angiogenesis is triggered by multiple angiogenic factors. Vascular endothelial growth factor blockers are currently a major mechanism of angiogenesis inhibition; however, either insensitivity due to the targeting of single angiogenic factors or serious side effects due to non-specific exposure ultimately leads to the failure of treatment. The herb-derived compound triptolide (TP) can inhibit tumor growth through multiple mechanisms. However, its hydrophobicity and side effects have hindered its translation to the clinic. Here, we have prepared TP-polymeric micelles (TP-PMs) using methoxy poly(ethylene glycol)–block–poly(ε-caprolactone). The drug loading efficiency and encapsulation efficiency can reach 7.2±0.10% and 99.1±1.05%, respectively. The TP-PM solution consisted of monodispersed particles (PDI = 0.100±0.023), which were 53.1±1.2 nm in size. In vitro release profiles indicated that the TP-PM solution exhibited better sustained-release action when compared with free TP solution. Pharmacokinetic and tumor tissue distribution studies showed that TP-PMs facilitated TP accumulation in tumor tissues. The tumor inhibition rate upon treatment with TP-PMs was higher than 50%, and the survival time of B16-F10 melanoma bearing mice was efficiently prolonged after TP-PM administration. In addition, serum VEGF levels and tumor incidence of the TP-PM-treated group were both significantly reduced, and histological analyses revealed that the tumor vessel diameter and density in the TP-PM-treated group were much smaller than those observed in the control groups. These results indicated that TP-PMs serve as a potential angiogenesis inhibitor.
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Document Type: Research Article
Publication date: May 1, 2015
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- Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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