Self-assembled dehydropeptide nanocarrier as a delivery system for antitumor drug temozolomide

Tong Wang; Qian Meng; Lan Lin; Li Yang; Wenjiao Zhao; Dequn Sun

doi:10.1016/j.bioorg.2022.105842

Self-assembled dehydropeptide nanocarrier as a delivery system for antitumor drug temozolomide

Bioorg Chem. 2022 Jul:124:105842. doi: 10.1016/j.bioorg.2022.105842. Epub 2022 Apr 27.

Authors

Tong Wang¹, Qian Meng², Lan Lin¹, Li Yang¹, Wenjiao Zhao³, Dequn Sun⁴

Affiliations

¹ School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China.
² Marine College, Shandong University at Weihai, Weihai, China.
³ School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China; Marine College, Shandong University at Weihai, Weihai, China.
⁴ School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China. Electronic address: dqsun@swust.edu.cn.

PMID: 35512421
DOI: 10.1016/j.bioorg.2022.105842

Abstract

Stable molecular conformation and intermolecular forces are essential for peptide self-assembly. In this study, one novel dehydropeptide (DDP) monomer (Boc-(Z)C^α,β-ΔPhe-Gly-NHMe, DDP 1) was prepared; its conformation was confirmed to be more stable than the normal peptide 2 by nuclear magnetic resonance (NMR) and X-ray crystal diffraction experiments. DDP 1 was self-assembled to one novel dehydropeptide nanomaterial (DDPN 1). Fourier transform infrared (FTIR) spectroscopy results showed that hydrogen bonding was the main driving force of self-assembly. Electron microscope images displayed that the DDPN 1 fibers were longer and more stable than peptide 2 nanomaterials. Results of cell activity and enzyme hydrolysis proved that DDPN 1 had excellent biocompatibility and resistance to the enzymatic hydrolysis of protease K. Therefore, the DDPN 1 was used to load the antitumor drug temozolomide (TMZ). Due to intermolecular hydrogen bonds formed between TMZ and DDPN 1, TMZ-loaded DDPN 1 had a high percent entrapment efficiency (EE) of 83.72 ± 4.30% (n = 8) and a percent drug loading efficiency (LE) of 6.70 ± 0.34% (n = 8), and the half-life of TMZ-loaded DDPN 1 was 2.5-3 times longer than that of TMZ at pH 7. The in vitro cell viability results revealed that TMZ-loaded DDPN 1 exhibited higher antitumor activity (IC₅₀ = 552.1 μM) against U118-MG than that of TMZ (IC₅₀ = 1980.1 μM), possibly because that U118-MG cells uptook more TMZ from TMZ-loaded DDPN 1 than from free TMZ directly. This study is expected to inspire the design of biocompatible nanocarriers applied for anti-enzymatic hydrolysis in drug delivery systems.

Keywords: Dehydropeptide; Drug delivery; Nanocarrier; Self-assembly; Temozolomide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Drug Delivery Systems / methods
Peptides / chemistry
Temozolomide / pharmacology

Substances

Antineoplastic Agents
Peptides
Temozolomide