Synergistically Enhanced Antimetastasis Effects by Honokiol-Loaded pH-Sensitive Polymer-Doxorubicin Conjugate Micelles

ACS Applied Materials & Interfaces
Yang ZouYan Liu

Abstract

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 a...Continue Reading

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Citations

Oct 31, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jing QuQing-Han Zhou
Jul 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xavier MontanéBartosz Tylkowski
Jul 17, 2021·European Journal of Pharmacology·Sepideh MirzaeiSaeed Samarghandian
Oct 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Raut BholakantJan Feijen

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