Hyaluronic Acid-Modified Cationic Nanoparticles Overcome Enzyme CYP1B1-Mediated Breast Cancer Multidrug Resistance

Abstract

Aim: Enzyme CYP1B1 (CYP1B1) is usually overexpressed in multidrug resistance (MDR) breast cancer cells, which could metabolically inactivate docetaxel (DTX). Materials & methods: The cationic core–shell nanoparticles (hyaluronic acid/polyethyleneimine nanoparticles [HA/PEI NPs]) modified with hyaluronic acid (HA) were developed and coloaded with DTX and α-napthtoflavone (ANF, a CYP1B1 inhibitor) to overcome MDR in breast cancer induced by CYP1B1. Physicochemical characterization, MDR reversing effect in vitro and pharmacokinetics in vivo of HA/PEI NPs were evaluated. Results: The HA/PEI NPs exhibited spherical morphology with size of (193.6 ± 3.1) nm. The HA/PEI NPs could reverse MDR effectively by downregulating the expression of CYP1B1. The HA/PEI NPs improved the bioavailability of DTX. Conclusion: The HA/PEI NPs might be a promising strategy to overcome CYP1B1-mediated breast cancer MDR.

Keywords::

• α-napthtoflavone
• breast cancer
• CD44
• CYP1B1
• DTX
• hyaluronic acid
• lysosome escape
• multidrug resistance
• nanoparticles
• polyethyleneimine

Financial & competing interests disclosure

The authors state that they have obtained appropriate institutional review board approval. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The animal experimental protocols were performed according to the guidelines of the Experimental Animal Ethics Committee of Shanghai Jiao Tong University. And they have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The authors state that they have obtained appropriate institutional review board approval. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.