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

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, the in vitro results 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.

Naked and Decorated Nanoparticles Containing H2S-Releasing Doxorubicin: Preparation, Characterization and Assessment of Their Antitumoral Efficiency on Various Resistant Tumor Cells

“…The effect was more pronounced with HA-NP-CTAB-H 2 S-DOXO than with NP-H 2 S-DOXO 3% PVP, likely because HA grants an active targeting of the NPs. Indeed, the HA receptor, CD44, has been detected in U-2OS/DX580 and K7M2 cells [ 16 ], and is also expressed in breast cancer as MDA-MB-231 cells [ 33 ]. These effects were not species-specific, as the higher accumulation was observed both in human and murine cell lines.…”

Research Progress of Bioinspired Nanostructured Systems for the Treatment of Ocular Disorders

“…The target nanocarrier modified by the variety of different CD44 ligands including the CD44 antibodies, peptide, hyaluronic acid, chitosan, and chondroitin sulfate have been established for the therapy of tumors [ 67 ]. In our previous studies, the CD44 peptide modified polymer micelles [ 68 ] and chitosan functionalized liposomes [ 69 , 70 ] were successfully synthesized and have shown an excellent in vivo and in vitro anti-tumor effect compared with the non-target nanocarriers.…”

Emodin as an Inhibitor of PRV Infection In Vitro and In Vivo

“…Especially in terms of antiviral properties, it has been shown to have a variety of antiviral activities, including against herpes simplex virus, SARS coronavirus, influenza A virus and porcine reproductive and respiratory syndrome virus [ 17 , 18 , 19 , 20 ]. Emodin has problems such as poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, which lead to an unsatisfactory therapeutic effect [ 21 ]. Despite these important advances, the antiviral activity of emodin against PRV has not been studied.…”