浙江科技学院孙婷婷团队揭示了二苯基丙氨酸类似物与乙二胺连接体自组装的介观模拟。这一研究成果发表在2025年3月11日出版的国际学术期刊《中国高分子科学杂志》上。

为了在分子水平上了解PA聚集体的组装途径、药物装载行为和形成机制，研究小组对PA分子系统进行了耗散粒子动力学（DPD）模拟。他们的模拟结果表明，PA分子自发组装成纳米球，并且在添加抗癌化疗药物阿霉素（DOX）后可以自组装成载药纳米球。该研究团队还发现PA分子的疏水侧链珠在纳米球内呈现出独特的洋葱状分布，这在实验中没有观察到。通过计算DPD微球的径向分布函数（RDF），验证了所制备的洋葱状纳米球。

此外，基于不同相互作用组分在总非键能中的百分比分析，PA分子间的主链-侧链相互作用可能在类洋葱纳米球的形成中起重要作用，主链-侧链、主链-药物、侧链-药物和主链-溶剂相互作用的协同作用在载药纳米球的形成中起重要作用。这些发现对PA的结构和自组装途径提供了新的认识，可能有助于设计高效的给药系统。

据悉，二苯丙氨酸及其类似物因其完美的自组装特性在生物学、医学和纳米技术等领域受到广泛关注。实验研究表明，具有乙二胺连接体的二苯基丙氨酸类似物（PA, P =苯丙氨酸，A =类似物）可以自组装成球形，可以作为新型抗癌药物载体。

附：英文原文

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

Author: Xin-Yi Zhao, Si-Qi Sun, Ning Zhou, Xiao-Jun Xu, Yan Wang, Ting-Ting Sun

Issue&Volume: 2025-03-11

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.

DOI: 10.1007/s10118-025-3300-3

Source: https://www.cjps.org/en/article/doi/10.1007/s10118-025-3300-3/