Zou, Yang Zhou, Yuanhang Jin, Yao He, Chuyu Deng, Yunqiang Han, Shidi Zhou, Chuhang Li, Xinru Zhou, Yanxia Liu, Yan Synergistically Enhanced Antimetastasis Effects by Honokiol-Loaded pH-Sensitive Polymer–Doxorubicin Conjugate Micelles In an effort to prevent metastasis of breast tumor cells- at the same time of inhibiting tumor growth with less toxic side effects, honokiol (HNK) was encapsulated into pH-sensitive polymeric micelles based on the conjugate of poly­(2-ethyl-2-oxazoline)-poly­(d,l-lactide) (PEOz-PLA) with doxorubicin (DOX), denoted as PEOz-PLA-imi-DOX. PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of PEOz-PLA via acid-cleavable benzoic imine linker. HNK-loaded conjugate micelles (HNK/PP-DOX-PM) with a size of 21 nm and homogeneous spherical shape exhibited high drug-loading capacity. PEOz-PLA-imi-DOX and HNK/PP-DOX-PM displayed faster release of DOX at pH 5.0 than at pH 7.4. As anticipated, PEOz-PLA-imi-DOX maintained cytotoxicity of DOX against MDA-MB-231 cells. The synergistically enhanced in vitro antitumor effect of HNK/PP-DOX-PM was confirmed by their synergetic inhibition of MDA-MB-231 cell growth. Furthermore, the efficient prevention of tumor metastasis by HNK/PP-DOX-PM was testified by in vitro anti-invasion, wound healing and antimigration assessment in MDA-MB-231 cells, and in vivo bioluminescence imaging in nude mice. The suppression of growth and metastasis of tumor cells by HNK/PP-DOX-PM was attributed to the synergistic effect of pH-triggered drug release and HNK-aroused inhibition of matrix metalloproteinases and epithelial–mesenchymal transition, respectively. In addition, HNK/PP-DOX-PM exhibited superior biosafety than physically encapsulated dual-drug micelles. Consequently, the fabricated HNK/PP-DOX-PM may have great potential for safe and effective suppression of tumor growth and metastasis. pH-triggered drug release;encapsulated dual-drug micelles;DOX;breast tumor cells;PEOz-PLA-imi-DOX;Synergistically Enhanced Antimetastasis Effects;vivo bioluminescence imaging;acid-cleavable benzoic imine linker;HNK-loaded conjugate micelles;MDA-MB -231 cell growth;tumor growth;MDA-MB -231 cells 2018-05-11
    https://acs.figshare.com/articles/journal_contribution/Synergistically_Enhanced_Antimetastasis_Effects_by_Honokiol-Loaded_pH-Sensitive_Polymer_Doxorubicin_Conjugate_Micelles/6329312
10.1021/acsami.8b04854.s001