Design and evaluation of glutathione responsive glycosylated camptothecin nanosupramolecular prodrug

Abstract

A novel tumor-targeted glutathione responsive Glycosylated-Camptothecin nanosupramolecular prodrug (CPT-GL NSp) was designed and fabricated via a disulfide bond. The effects of glycoligand with different polarities on solubility, self-assembly, stability, cellular uptake, and glutathione responsive cleaving were explored, and an optimal glycosylated ligand was selected for nanosupramolecular prodrug. It has been found that CPT-GL NSp exhibited higher drug loading than traditional nanoparticles. Among of which maltose modified NSp had the strongest anti-tumor effects than that of glucose and maltotriose. CPT-SS-Maltose had a similar anti-tumor ability to Irinotecan (IR), but the superior performance in solubility, hemolysis, and uptake of HepG2 cells.

Keywords:

• Glutathione
• camptothecin
• glycosylated
• nanosupramolecular prodrug
• anti-tumor ability

Author contributions

Changmei Zhang and Haisheng Peng designed the overall project, and Wenhua Li and Zhong Chen carried out all the experiments. Other authors participated in some related experiments.

Disclosure statement

All authors declared no conflicts of interest.

Additional information

Funding

This research was financially supported by Fundamental Research Funds for the Provincial Universities of Heilongjiang Province [No. 2017JCZX08], the Scientific Research Fund of Harbin Medical University-Daqing [No. DQXN201603], Doctor groundbreaking Foundation of Harbin Medical University-Daqing [No. 2019]. Technological Innovation Center for Precision Diagnosis and Treatment of Diseases in Cold Regions of Heilongjiang Province-Achievement Transformation and cultivation Project [CXZX-ZXKT02 and CXZX-ZXKT03].