Tomalia Donald A
The National Dendrimer & Nanotechnology Center, NanoSynthons LLC, Mt. Pleasant, MI 48858, USA.
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pharmaceutics. 2024 Nov 28;16(12):1530. doi: 10.3390/pharmaceutics16121530.
This perspective begins with an overview of the major impact that the dendron, dendrimer, and dendritic state (DDDS) discovery has made on traditional polymer science. The entire DDDS technology is underpinned by an unprecedented new polymerization strategy referred to as step-growth, amplification-controlled polymerization (SGACP). This new SGACP paradigm allows for routine polymerization of common monomers and organic materials into precise monodispersed, dendritic macromolecules (i.e., dendrons/dendrimers) with nanoscale sizes and structure-controlled features that match and rival discrete in vivo biopolymers such as proteins and nucleic acids (i.e., DNA, siRNA, mRNA, etc.). These dendritic architectures exhibit unprecedented new intrinsic properties widely recognized to define a new fourth major polymer architecture class, namely: Category (IV): dendrons, dendrimers, and random hyperbranched polymers after traditional categories: (I) linear, (II) cross-linked, and (III) simple-branched types. Historical confusion over the first examples of the structure confirmed and verified cascade, dendron, dendrimer, and arborol syntheses, while associated misuse of accepted dendritic terminology is also reviewed and clarified. The importance of classifying all dendrons and dendrimers based on branch cell symmetry and the significant role of critical nanoscale-design parameters (CNDPs) for optimizing dendritic products for pharma/nanomedicine applications with a focus on enhancing stealth, non-complement activation properties is presented. This is followed by an overview of the extraordinary growth observed for amphiphilic dendron/dendrimer syntheses and their self-assembly into dendritic supramolecular assemblies, as well as many unique applications demonstrated in pharma and nanomedicine, especially involving siRNA delivery and mRNA vaccine development. This perspective is concluded with optimistic expectations predicted for new dendron and dendrimer application roles in pharma, nanomedicine, and life sciences.
本文首先概述了树枝状分子、树枝状聚合物和树枝状结构状态（DDDS）的发现对传统聚合物科学产生的重大影响。整个DDDS技术基于一种前所未有的新型聚合策略，即逐步增长、扩增控制聚合（SGACP）。这种新的SGACP范式允许将常见单体和有机材料常规聚合成精确的单分散树枝状大分子（即树枝状分子/树枝状聚合物），其具有纳米级尺寸和结构可控的特征，可与体内离散的生物聚合物如蛋白质和核酸（即DNA、siRNA、mRNA等）相媲美。这些树枝状结构展现出前所未有的新内在特性，被广泛认为定义了一种新的第四大主要聚合物结构类别，即：类别（IV）：在传统类别（I）线性、（II）交联和（III）简单分支类型之后的树枝状分子、树枝状聚合物和无规超支化聚合物。还回顾并澄清了关于已确认和验证的级联、树枝状分子、树枝状聚合物和树状醇合成的首个实例的历史混淆，以及相关的对公认树枝状术语的误用。介绍了基于分支单元对称性对所有树枝状分子和树枝状聚合物进行分类的重要性，以及关键纳米级设计参数（CNDPs）对于优化用于制药/纳米医学应用的树枝状产品的重要作用，重点是增强隐身性、非补体激活特性。接着概述了两亲性树枝状分子/树枝状聚合物合成中观察到的显著增长及其自组装成树枝状超分子组装体，以及在制药和纳米医学中展示的许多独特应用，特别是涉及siRNA递送和mRNA疫苗开发。本文最后对树枝状分子和树枝状聚合物在制药、纳米医学和生命科学中的新应用角色给出了乐观预期。
