Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

Abstract

Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy.

Keywords:

• apoptosis
• liver cancer
• drug delivery
• antitumor

Supplementary materials

Figure S1 Bar graph of the size of nanoparticles.

Figure S2 Fluorescent intensity of FITC detected by FACS.

Abbreviations: NP, nanoparticle; FITC, fluorescein isothiocyanate; FACS, fluorescence-activated cell sorting.

Figure S3 H&E staining of different tissues in mice from different groups of mice.

Abbreviations: NP, nanoparticle; UA, ursolic acid; UA-NPs, UA-loaded poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles; H&E, hematoxylin and eosin.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant numbers 81372659, 81001077, and 81270817), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

We thank Ms Maureen Aliru from University of Texas MD Anderson Cancer Center for proofreading the manuscript.

Disclosure

The authors report no conflicts of interest in this work.