A novel pH-sensitive carrier for the delivery of antitumor drugs: histidine-modified auricularia auricular polysaccharide nano-micelles

Abstract

The study was aimed to design a novel pH-sensitive carrier to deliver antitumor drugs to increase treatment efficiency. Histidine (His)was used to modify auricularia auricular polysaccharide (AAP) by esterification. Proton nuclear magnetic resonance spectrometry was developed to characterize the His-AAP carrier and the His-AAP Paclitaxel (PTX) micelles were prepared by self-assembled organic solvent evaporation. The formation of His-AAP PTX micelles was confirmed by dynamic light-scattering, transmission electron microscopy and high performance liquid chromatography. It was found that the His-AAP PTX micelles possessed a spherical morphology with an average diameter of 157.2 nm and an 80.3% PTX encapsulation efficiency. In vitro release at pH 7.4, 6.5, 5.0 reached 70%, 71%, and 88%, respectively. The cell viability assay and confocal laser scanning microscope were used to evaluate the cytotoxicity and cell uptake of the His-AAP PTX micelles. Compared with Taxol, the IC50 of the His-AAP PTX micelles were lower after incubating for 24 h, 48 h, or 72 h (0.216 versus 0.199, 0.065 versus 0.060, and 0.023 versus 0.005, respectively). In a test of tumor-bearing mice, the His-AAP PTX micelles significantly inhibited tumor growth. These results showed that His-AAP PTX micelles are a highly promising therapeutic system for anticancer therapy.

Micelles Based on Lysine, Histidine, or Arginine: Designing Structures for Enhanced Drug Delivery

“…The simplest way to develop micelles containing histidine is to attach hydrophobic histidine to hydrophilic macromolecules, such as hyaluronic acid ( Wu et al, 2016 ), dextran ( Yin et al, 2020 ), and auricularia auricular polysaccharide (AAP) ( Wang et al, 2017 ). In the above micelles, histidine is usually used as a micellar core.…”

“…Next, paclitaxel was loaded into His-AAP micelles. Compared to that at pH 7.4, the paclitaxel accumulated release rate was increased by about 18% for 12 h at pH 5.0 ( Wang et al, 2017 ). Research by Chang et al (2010) also confirmed that micelles based on histidine had the characteristic of pH-sensitive drug release.…”

Structure and radio‐protective effects of sulfated Auricularia auricula polysaccharides

“…A. auricular lacks cholesterol and is relatively rich in polysaccharides, minerals, and protein (Zheng et al, ). This mushroom has been shown to prevent thrombosis (Fan et al, ), tumors (Ma, Wang, Zhang, Zhang, & Ding, ), and to reduce cytotoxicity (Wang et al, ) and oxidative damage (Oke & Aslim, ) and to have an antiradiation effect (Xun et al, ).…”

Ultrasound-facilitated assembly and disassembly of a pH-sensitive self-assembly peptide

“…Trigger by pH is one of the well-explored internal stimuli, especially in the drug delivery eld. 11,12 For the intracellular delivery of therapeutics, upon endocytosis, cargoes and carriers usually experience a pH drop during intracellular trafficking, from neutral ($pH 7.4) extracellular environment to slightly acidic ($pH 6.5) in early endosome, then more acidic ($pH 5.5) late endosome and nally lysosome ($pH 4.5).…”

“…11,14 Ultrasound is one of the noninvasive external stimuli, which is able to enhance/disrupt or recongure the peptide self-assemblies through adjustable mechanical perturbation. For example, short brils of 20-100 nm could be generated through ultra-sonication of mature brils, 15 which is a routine method to make self-assembly seeds.…”