Department of Fiber and Polymer Technology, The School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Teknikringen 56-58, SE-100 44 Stockholm, Sweden.
Biomacromolecules. 2020 Oct 12;21(10):4273-4279. doi: 10.1021/acs.biomac.0c01068. Epub 2020 Sep 11.
Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of ABC monomers, amalgamated from two traditional AB monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.
具有内部和外部功能表示的杂化树突状聚合物被认为是最终的树突状结构。这反映在它们前所未有的支架中，例如可以精确控制整个树突骨架上不同载物的结构、分子量、数量和位置。因此，这些具有多功能特性的树突状聚合物是精确聚合物的巅峰之作，并且由于它们可以在许多前沿应用中找到用途，尤其是作为治疗用途的离散单分子载体，因此对科学界极具吸引力。不幸的是，大多数已建立的树突状聚合物家族仅具有外部功能，但缺乏内部支架能力，这导致其作为精确载体的全部潜力受到固有限制。因此，在这里，我们采用了一种新的合成策略，便于在已建立的树突状聚合物中引入内部功能化。作为概念验证，通过巧妙而简单的 ABC 单体设计，成功获得了一类基于已建立的 2,2-双（羟甲基）丙酸（bis-MPA）的新型内部和外部功能化多功能树突状聚合物。利用氟化物促进的酯化反应（FPE），在不到一天的反应时间内，通过逐步发散生长至第四代，成功地实现了分子量为 15 kDa，并且显示出 93 个可反应基团，分为 45 个内部和 48 个外部功能基团。通过点击反应进行后功能化的可行性得到了证明，其中可以快速有效地连接药物、染料和 PEG 链，并且可以交联成多功能水凝胶。所提出的策略的简单性和多功能性可以很容易地转化为生成各种功能材料，例如聚合物、表面、纳米粒子或生物分子。
