4 years ago

A Self-assembly Nanodrug Delivery System Based on Amphiphilic Low Generations of PAMAM Dendrimers-Ursolic Acid Conjugate Modified by Lactobionic Acid for HCC Targeting Therapy.

Yan Guo, Ruirui Zhao, Kai Jiang, Bowen Li, Zhichun Shen, Jingwei Shao, Lulu Fan, Guirong Zheng, Yajun Liu
Ursolic acid (UA), a natural triterpene acids, is a promising anti-cancer drug due to its inhibitory effect on tumor growth and metastasis. However, clinical translation of UA is limited by its poor water solubility and low bioavailability. To overcome these problems, herein an amphiphilic self-assembly nanodrug composed of UA, lactobionic acid (LA) and low-polyamidoamine (low-PAMAM) dendrimers is developed. This near-spherical nanodrug with a uniform size (~180nm) demonstrated to have an enhanced cytotoxicity against liver cancer SMMC7721 cells, and could attenuate the migration and adhesion of SMMC7721 cells at non-toxic concentrations by suppressing metastasis-related protein MMP-9 expression. Furthermore, in vivo study indicates that the nanodrug exhibited prolonged circulation time in blood as well as increased AUC, MRT and Cmax, and could effectively inhibit the tumor growth in H22 mice model. Overall, the UA-based nanodrug delivery system reported in the present work represents a novel strategy for targeted tumor therapy.

Publisher URL: http://doi.org/10.1016/j.nano.2017.10.007

DOI: 10.1016/j.nano.2017.10.007

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