10.1007/s40097-023-00523-7

Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems

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  • Pasqualina Liana Scognamiglio1,
  • Claudia Riccardi2,
  • Rosanna Palumbo3,
  • Thomas F. Gale4,
  • Domenica Musumeci5,
  • Giovanni N. Roviello*3,
  1. Centre for Advanced Biomaterial for Health Care (CABHC), Italian Institute of Technology, Naples, 80125, IT Department of Chemical, Materials and Production Engineering (DICMAPI), University of Naples Federico II, Naples, 80125, IT
  2. Department of Chemical Sciences, University of Naples Federico II, Naples, 80126, IT
  3. Consiglio Nazionale delle Ricerche (CNR), Institute of Biostructure and Bioimaging (IBB), Naples, 80145, IT
  4. School of Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, GB
  5. Department of Chemical Sciences, University of Naples Federico II, Naples, 80126, IT Consiglio Nazionale delle Ricerche (CNR), Institute of Biostructure and Bioimaging (IBB), Naples, 80145, IT
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Published in Issue 10-02-2023

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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Scognamiglio, P. L., Riccardi, C., Palumbo, R., Gale, T. F., Musumeci, D., & Roviello, G. N. (2023). Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems. Journal of Nanostructure in Chemistry, 14(5). https://doi.org/10.1007/s40097-023-00523-7
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Abstract

Abstract The design, synthesis and characterization of a novel nucleoamino acid derivative based on an l -tryptophanamide functionalised with a thymine nucleobase (named TrpT) is here described. The novel construct’s tendency to self-assemble into supramolecular networks in aqueous solution was demonstrated by dynamic light scattering (DLS), circular dichroism (CD), fluorescence and UV spectroscopic measurements. TrpT nanoaggregates showed good stability (up to 5 h) at 140 µM and proved to comprise species of mean hydrodynamic diameter 330 nm and a homogeneous size distribution; scanning electron microscopy (SEM) analysis further revealed these to be spherical-shaped assemblies. The ability of TrpT nanoaggregates to bind curcumin, selected as a model anticancer drug, was also evaluated and its release was monitored over time by confocal microscopy. Molecular docking studies were performed on both TrpT self-assembly and curcumin-loaded nanoaggregates suggesting that the phytomolecule can be accommodated in the interior of the supramolecular network via hydrophobic ( π − π and π -alkyl) interactions; the formation of TrpT-curcumin adducts may improve the polarity of the highly-hydrophobic curcumin with a resulting logP closer to the optimal values expected for a good drug bioavailability, as estimated by the ADMETlab software. Finally, the high stability of TrpT nanoassembly in human serum, and the absence of significant toxic effects on human model cells in a cell viability assay, were also demonstrated. Despite its thymine-based scaffold, TrpT was shown not to bind adenine-bearing nucleic acids, suggesting that this interaction is hindered by its intrinsic propensity to self-assemble in preference to forming A-T base pairings. Instead, TrpT was able to interact with a serum protein such as bovine serum albumin (BSA), known to improve the bloodstream transportation and bioavailability of its cargo. Collectively, our findings support the potential use of TrpT for the development of new drug delivery systems. Graphical abstract

Keywords

  • Nucleoamino acids,
  • Thyminyl tryptophanamide,
  • Self-assembly,
  • Nanosystems,
  • Serum stability,
  • Drug delivery,
  • Molecular docking,
  • Self-docking
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