pH-responsive and CD44-targeting polymer micelles based on CD44p-conjugated amphiphilic block copolymer PEG- b-HES- b-PLA for delivery of emodin to breast cancer cells

Nanotechnology. 2022 Apr 20;33(27). doi: 10.1088/1361-6528/ac5f9a.

Abstract

Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, thein vitroresults showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.

Keywords: CD44; breast cancer; pH-responsive; polyethylene glycol; polymeric micelles.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Drug Carriers
  • Drug Delivery Systems
  • Emodin*
  • Female
  • Humans
  • Hyaluronan Receptors
  • Hydrogen-Ion Concentration
  • Micelles
  • Polyesters
  • Polyethylene Glycols
  • Polymers

Substances

  • CD44 protein, human
  • Drug Carriers
  • Hyaluronan Receptors
  • Micelles
  • Polyesters
  • Polymers
  • Polyethylene Glycols
  • Emodin