Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, United States.
Wisconsin Center for NanoBioSystems, University of Wisconsin, Madison, Wisconsin 53705, United States.
Bioconjug Chem. 2022 Nov 16;33(11):2008-2017. doi: 10.1021/acs.bioconjchem.2c00128. Epub 2022 May 5.
Polymers constitute a diverse class of macromolecules that have demonstrated their unique advantages to be utilized for drug or gene delivery applications. In particular, polymers with a highly ordered, hyperbranched structure─"dendrons"─offer significant benefits to the design of such nanomedicines. The incorporation of dendrons into block copolymer micelles can endow various unique properties that are not typically observed from linear polymer counterparts. Specifically, the dendritic structure induces the conical shape of unimers that form micelles, thereby improving the thermodynamic stability and achieving a low critical micelle concentration (CMC). Furthermore, through a high density of highly ordered functional groups, dendrons can enhance gene complexation, drug loading, and stimuli-responsive behavior. In addition, outward-branching dendrons can support a high density of nonfouling polymers, such as poly(ethylene glycol), for serum stability and variable densities of multifunctional groups for multivalent cellular targeting and interactions. In this paper, we review the design considerations for dendron-lipid nanoparticles and dendron micelles formed from amphiphilic block copolymers intended for gene transfection and cancer drug delivery applications. These technologies are early in preclinical development and, as with other nanomedicines, face many obstacles on the way to clinical adoption. Nevertheless, the utility of dendron micelles for drug delivery remains relatively underexplored, and we believe there are significant and dramatic advancements to be made in tumor targeting with these platforms.
聚合物构成了一大类具有独特优势的大分子，可用于药物或基因递送应用。特别是具有高度有序、超支化结构的聚合物——“树枝状大分子”——为这类纳米药物的设计提供了显著的优势。树枝状大分子被引入嵌段共聚物胶束中，可以赋予各种独特的性质，这些性质通常在线性聚合物对应物中观察不到。具体来说，树枝状结构诱导形成胶束的单体呈锥形，从而提高热力学稳定性并实现低临界胶束浓度（CMC）。此外，通过高密度的高度有序的官能团，树枝状大分子可以增强基因复合物、药物负载和刺激响应行为。此外，向外分支的树枝状大分子可以支持高密度的非缠结聚合物，如聚乙二醇，以提高血清稳定性和多功能基团的可变密度，实现多价细胞靶向和相互作用。在本文中，我们综述了用于基因转染和癌症药物递送应用的两亲性嵌段共聚物形成的树枝状脂质纳米粒和树枝状胶束的设计考虑因素。这些技术处于临床前开发的早期阶段，与其他纳米药物一样，在临床应用的道路上面临许多障碍。然而，树枝状胶束在药物递送方面的应用仍然相对未得到充分探索，我们相信在利用这些平台进行肿瘤靶向方面还有重大而显著的进展。
