Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker

Xin-Yi Zhao; Si-Qi Sun; Ning Zhou; Xiao-Jun Xu; Yan Wang; Ting-Ting Sun

doi:10.1007/s10118-025-3300-3

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Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker

RESEARCH ARTICLE | Updated：2025-07-14

- Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker
- Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker
- 高分子科学（英文） 2025年43卷第4期页码：666-676
- Affiliations：
  
  a.Department of Physics, Zhejiang University of Science and Technology, Hangzhou 310008, China
  b.Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou 213001, China
- Author bio：
  
  120086@zust.edu.cn (Y.W.)
  tingtingsun@zust.edu.cn (T.T.S.)
- Funds：
  
  This study was financially supported by the National Natural Science Foundation of China (Nos. 20904047 and 12074151) and the Natural Science Foundation of Zhejiang Province (Nos. LY17A040001 and LY19F03004).;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3300-3.
- DOI：10.1007/s10118-025-3300-3
  中图分类号：
- 收稿日期：2024-11-22，
  
  修回日期：2025-01-04，
  
  录用日期：2025-01-17，
  
  网络出版日期：2025-03-11，
  
  纸质出版日期：2025-04-01
- Accepted：
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Zhao, X. Y.; Sun, S. Q.; Zhou, N.; Xu, X. J.; Wang, Y.; Sun, T. T. Mesoscopic simulation on self-assembly of diphenylalanine-based analogue with ethylenediamine linker. Chinese J. Polym. Sci. 2025, 43, 666–676

Xin-Yi Zhao, Si-Qi Sun, Ning Zhou, et al. Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker[J]. Chinese journal of polymer science, 2025, 43(4): 666-676.
Zhao, X. Y.; Sun, S. Q.; Zhou, N.; Xu, X. J.; Wang, Y.; Sun, T. T. Mesoscopic simulation on self-assembly of diphenylalanine-based analogue with ethylenediamine linker. Chinese J. Polym. Sci. 2025, 43, 666–676 DOI： 10.1007/s10118-025-3300-3.

Xin-Yi Zhao, Si-Qi Sun, Ning Zhou, et al. Mesoscopic Simulation on Self-assembly of Diphenylalanine-based Analogue with Ethylenediamine Linker[J]. Chinese journal of polymer science, 2025, 43(4): 666-676. DOI： 10.1007/s10118-025-3300-3.

摘要

Diphenylalanine-based analogue with ethylenediamine linker (PA molecule) can self-assemble to form onion-like nanospheres

serving as highly effective carriers for cancer chemotherapeutic agents. And main chain-side chain interaction between PA molecules may be important in the formation of onion-like nanospheres.

Abstract

Diphenylalanine and its analogs cause many concerns owing to their perfect self-assembly properties in the fields of biology

medicine

and nanotechnology. Experimental research has shown that diphenylalanine-based analogs with ethylenediamine linkers (PA

P = phenylalanine

and A = analog) can self-assemble into spherical assemblies

which can serve as novel anticancer drug carriers. In this work

to understand the assembly pathways

drug loading behavior

and formation mechanism of PA aggregates at the molecular level

we carried out dissipative particle dynamics (DPD) simulations of PA molecule systems. Our simulation results demonstrate that PA molecules spontaneously assemble into nanospheres and can self-assemble into drug-loaded nanospheres upon addition of the cancer chemotherapeutic agent doxorubicin (DOX). We also found that the hydrophobic side chain beads of PA molecules exhibited a unique onion-like distribution inside the nanospheres

which was not observed in the experiment. The onion-like nanospheres were verified by calculating the radial distribution function (RDF) of the DPD beads. Furthermore

based on the analysis of the percentages of different interaction components in the total nonbonded energies

main chain-side chain interactions between PA molecules may be important in the formation of onion-like nanospheres

and the synergistic effects of main chain-side chain

main chain-drug

side chain-drug

and main chain-solvent interactions are significant in the formation of drug-loaded nanospheres. These findings provide new insights into the structure and self-assembly pathway of PA assemblies

which may be helpful for the design of efficient and effective drug delivery systems.

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