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.
Cheng
C
Wang
Ying
Y
Shan
Jiuli
J
Yang
Xuelian
X
Xu
Bo
B
Zhuang
Yingfang
Y
Fan
Wei
W
Xu
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002478:Cells, Cultured; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004337:Drug Carriers; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide