Civril Enfal, Sanyal Rana, Sanyal Amitav
Department of Chemistry, Bogazici University, Bebek, Istanbul, 34342, Turkiye,
Bogazici University Center for Targeted Therapy Technologies, Istanbul, 34684, Turkiye.
J Mater Chem B. 2026 Jan 7;14(1):12-44. doi: 10.1039/d5tb02193f.
In recent years, there has been remarkable progress in designing drug delivery systems since the dawn of polymer therapeutics. Advances in polymer science and bioconjugation chemistry continue to advance the design and efficiency of drug delivery systems. Among the various drug delivery systems, polymeric micelles stand out because of their versatile features, like increased bioavailability of hydrophobic therapeutic cargo, as well as enhanced uptake in tumors because of their nanosize-mediated passive targeting. Importantly, the polymeric micelles can be engineered to actively target disease sites through surface functionalization with appropriate bioactive ligands. Decorating the micelle surface with bioactive ligands has emerged as one of the most preferred approaches to enhance their targeting capability. Over the years, many ligands have been explored for active targeting, ranging from sugars and peptides to antibodies and oligonucleotides. Progress in protein sciences and molecular biology continues to reveal new ligands and enlarge this library. Considering the delicate nature of the biological ligands, the utilization of mild, efficient, and benign chemical transformations is vital. In this context, the advent of "click" chemistry has dramatically altered the design of targeted micelles. The ability to modify polymers with "clickable" handles at the desired locations, as well as control over the density of these reactive units, expands the utilization of this chemistry. Over the years, the focus has shifted from the highly efficient copper-catalyzed azide-alkyne cycloaddition to "metal-free click" reactions. Additionally, bioorthogonal "click" reactions have enabled the achievement of " click" transformation-based targeting strategies either through metabolic glycoengineering or stimuli-induced aggregation. This review focuses on the advances in the fabrication of ligand-based targeted micelles using the "click" reaction for ligand conjugation onto polymeric micelles and highlights recent applications of these materials for targeted drug delivery.
近年来，自聚合物治疗学诞生以来，药物递送系统的设计取得了显著进展。聚合物科学和生物共轭化学的进步不断推动药物递送系统的设计和效率提升。在各种药物递送系统中，聚合物胶束因其多功能特性脱颖而出，例如疏水性治疗药物的生物利用度提高，以及由于其纳米尺寸介导的被动靶向作用而增强了在肿瘤中的摄取。重要的是，聚合物胶束可以通过用适当的生物活性配体进行表面功能化来设计成主动靶向疾病部位。用生物活性配体修饰胶束表面已成为增强其靶向能力的最优选方法之一。多年来，人们探索了许多用于主动靶向的配体，从糖类、肽类到抗体和寡核苷酸。蛋白质科学和分子生物学的进展不断揭示新的配体并扩大这个库。考虑到生物配体的微妙性质，利用温和、高效且良性的化学转化至关重要。在这种背景下，“点击”化学的出现极大地改变了靶向胶束的设计。能够在所需位置用“可点击”手柄修饰聚合物，以及控制这些反应单元的密度，扩大了这种化学的应用范围。多年来，重点已从高效的铜催化叠氮化物 - 炔烃环加成反应转向“无金属点击”反应。此外，生物正交“点击”反应通过代谢糖工程或刺激诱导聚集实现了基于“点击”转化的靶向策略。本综述重点介绍了使用“点击”反应将配体缀合到聚合物胶束上制备基于配体的靶向胶束的进展，并突出了这些材料在靶向药物递送中的最新应用。
