Polymeric nanoparticles with complex architecture and composition: simulations and theory

水介质中两亲分子的自组织是生物体和自然界用于组装前所未有的复杂结构的通用机制。21世纪的主要科学挑战之一是揭示合成、生物和杂交大分子的自组织基本原理，并将这些知识应用于设计新型（包括仿生）功能纳米材料。高分子纳米胶体，包括星形聚合物、树状大分子、分子刷和两亲嵌段共聚物的自组装胶束，被广泛用作药物和遗传物质的纳米载体。近年来，更复杂的拓扑结构，如树突刷，枝状结构和杂化嵌段共聚物，包含线性和分支块或两个不同的分支块引起了广泛的关注。利用拓扑多样性使得药物和基因传递系统的分子设计取得了实质性进展，包括由于暴露于环境中的潜在功能化末端基团数量的增加而更积极地利用分子识别机制。虽然线性-线性嵌段共聚物的自组装得到了很好的理解，但缺乏关于一个或两个嵌段的分支对组装结构的影响的理论知识。我们的目标是在理论支持的多尺度计算机模型的基础上，研究分层支链大分子（枝晶）的构象以及由支链嵌段组成的两亲嵌段共聚物及其与吸收药物或核酸的小分子的配合物的自组装结构的性质。在我们的多尺度计算机模拟中使用的技术范围从原子和粗粒度分子和布朗动力学到耗散粒子动力学，反应系综MC方法和自洽场数值方法。这些技术的多样性将使我们能够在多个长度尺度上研究感兴趣的系统。最终，我们的目标是创建一个基于多尺度模拟的工具箱，用于新型药物和基因纳米载体的大分子设计，这将对治疗许多严重疾病的进展产生重大影响，包括癌症和神经退行性疾病。

The self-organization of amphiphilic molecules in aqueous media is a generic mechanism used by living organisms and nature to assembly structures of unprecedented complexity. Among major scientific challenges in the 21st century is the unravelling of fundamental principles of self-organization of synthetic, biological and hybrid macromolecules and applying this knowledge for the design of novel (including biomimetic) functional nanomaterials. Polymeric nano-colloids, including star-like polymers, dendrimers, molecular brushes and self-assembled micelles of amphiphilic block copolymers are widely used as nano-carries for delivery of drugs and genetic material. Recently, more topologically complex structures, such as dendron brushes, dendrigrafts and hybrid block copolymers containing linear and branched blocks or two different branched blocks have attracted considerable attention. The exploitation of topological diversity enables a substantial progress in molecular design of drug and gene delivery systems, including more active exploitation of molecular recognition mechanisms due to increasing number of potentially functionalized terminal groups exposed to the environment While self-assembly of linear-linear block copolymers is well understood, the theoretical knowledge about the effect of branching of one or both blocks on the assembled structures is lacking. We aim to study conformations of hierarchically branched macromolecules (dendrigrafts) as well as properties of self-assembled structures of amphiphilic block copolymers comprising branched blocks and their complexes with small molecules assimilating drugs or nucleic acids on the basis of multiscale computer modelling supported by theory. The spectrum of techniques used in our multiscale computer simulations ranges from atomistic and coarse-grained molecular and Brownian dynamics to dissipative particle dynamics, reaction ensemble MC methods and self-consistent field numerical methods. The complete variety of such techniques will enable us to study systems of interest on multiple length scales. Ultimately, we aim to create a multiscale simulation-based toolbox for macromolecular design of novel drug and gene nano-carries that will have a substantial impact on the progress of treating many serious diseases, including cancer and neurodegenerative diseases.