Polymeric nanoparticles with complex architecture and composition: simulations and theory

两亲分子在水介质中的自组织是生物体和自然界用来组装前所未有的复杂结构的一般机制。世纪的主要科学挑战之一是揭示合成、生物和混合大分子自组织的基本原理，并将这些知识应用于新型（包括仿生）功能纳米材料的设计。聚合物纳米胶体，包括星形聚合物、树枝状聚合物、分子刷和两亲性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，拓扑结构更加复杂的结构，如树枝状刷，树枝状接枝和混合嵌段共聚物含有线性和支化嵌段或两个不同的支化嵌段引起了人们的极大关注。拓扑多样性的利用使得药物和基因递送系统的分子设计能够取得实质性进展，包括由于暴露于环境的潜在官能化末端基团的数量增加而更积极地利用分子识别机制。缺乏关于一个或两个嵌段的支化对组装结构的影响的理论知识。我们的目标是研究的构象的分级支化的大分子（树枝状接枝），以及自组装结构的两亲性嵌段共聚物，包括支化的嵌段和它们的复合物与小分子同化药物或核酸的理论支持的多尺度计算机建模的基础上的性能。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的分子和布朗动力学耗散粒子动力学，反应系综MC方法和自洽场数值方法。这些技术的完整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.