Abstract

Dopamine-modified hyaluronic acid (HA-DOP) was chosen as the drug carrier in this study, and Cu2+ was selected from among Cu2+, Zn2+, Fe2+, and Ca2+ as the central atom. 6-Mercaptopurine (6-MP) was conjugated with HA through a coordination reaction. HA-DOP-copper-MP (HA-DOP-Cu-MP), a redox-responsive coordination polymer prodrug, was prepared. The drug loading was 49.5 mg/g, the encapsulation efficiency was 70.18%, and the particle size was 173.5 nm. HA-DOP-Cu-MP released rapidly in the release medium containing reduced glutathione (GSH), and the accumulated release exceeded 94% in 2 h. In the release medium without GSH, the drug release rate was slow, with only 15% of the 6-MP released in 24 h. Cell uptake experiments revealed the CD44 targeting of HA. Cell viability assays showed that the cytotoxicity of HA-DOP-Cu-MP was higher than that of free 6-MP. Indeed, HA-DOP-Cu-MP is very toxic to cancer cells. In this paper, the redox-responsive drug delivery system was synthesized by a coordination reaction. The tumour targeting and tumour cytotoxicity of 6-MP were improved.

Highlights

  • Cancer is the primary cause of morbidity and mortality worldwide

  • When the hyaluronic acid (HA)-DOP-Cu-MP coordination polymer was internalized by tumour cells, 6-MP was released in the presence of GSH, killing the tumour cells (Figure 2)

  • These changes can be used to determine whether the metal ion is coordinated with ligand.ppm were assigned to the protons of the dopamine moiety

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Summary

Introduction

Cancer is the primary cause of morbidity and mortality worldwide. The pharmaceutical industry has invented many cytotoxic drugs that could potentially cure cancer. The strength of the bonds between dopamine and metal ions (0.8 nN) is similar to the typical strength of a covalent bond (2 nN) [24] This characteristic is why dopamine is widely used to modify polymers for drug delivery, such as poly (ethylene glycol) (PEG), chitosan, mesoporous silica, and hyaluronic acid (HA). 6-MP has the shortcomings of systemic toxic side effects, a short half-life, low bioavailability, and gastrointestinal reactions after oral administration [34] To avoid these shortcomings and increase the water solubility and efficacy of 6-MP, we chose HA as the carrier and modified it with dopamine to enhance its coordination ability. When the HA-DOP-Cu-MP coordination polymer was internalized by tumour cells, 6-MP was released in the presence of GSH, killing the tumour cells (Figure 2).

Materials
Synthesis of HA-DOP
Characterization of the 1 H-NMR Spectrum
Drug Release Experiment
Cell Uptake Assay
Cell Viability Assays
Synthetic Method
Particle size of HA-DOP-Cu-MP
FT-IR Spectroscopy Measurement
Conclusions
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