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

Yingying Wang,Qihao Xu,Xinggang Yang,Fen Chen,Lianqun Jia,Weisan Pan,Yanyao Liang,Mengqi Liu,Xiumei Gai,Pingfei Li,Yibin Yu,Zhihong Zhu,Yan Di

doi:10.1038/s41598-017-04428-8

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.

Highlights

The study was aimed to design a novel pH-sensitive carrier to deliver antitumor drugs to increase treatment efficiency
The auricular polysaccharide (AAP) and Histidine-modified Auricularia auricular polysaccharide (His-AAP) structures were identified by proton nuclear magnetic resonance (1H NMR) spectroscopy (Fig. 1B and C)
The tumor inhibition rate (TIR) value of the His-AAP PTX micelles group was found to be 84.2%, while the TIR value of the Taxol group was 54.6%. These results indicate that the His-AAP PTX micelles group exhibited an excellent antitumor effect and lower side-effects

Summary

Introduction

The study was aimed to design a novel pH-sensitive carrier to deliver antitumor drugs to increase treatment efficiency. In a test of tumor-bearing mice, the His-AAP PTX micelles significantly inhibited tumor growth. Because of its water solubility, it cannot be used alone as a drug delivery carrier To solve this problem, in our previous work, we combined AAP with chitosan (CS) using the polyelectrolyte complexes (PEC) method to prepare AAP-CS-NPs for the delivery of Doxorubicin (DOX)[22]. We found that AAP-CS-Nanoparticles can only deliver hydrophilic drugs and release more drugs at pH7.4 than that at pH 5.0 This is important since it is known that an acidic pH is the common microenvironment in solid tumors, and the interstitial fluid in tumors has a lower pH than normal tissues (6.75 vs 7.23), while the pH of endosomes and lysosomes is 5.0~5525, 26. Because of the microenvironment of tumors, we developed a novel type of nano-micelles which was pH-sensitive

Methods

Results

Conclusion