Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel.
The Center for Nanoscience and Nanotechnology, Tel-Aviv University, Tel-Aviv, Israel.
J Mater Chem B. 2024 Nov 20;12(45):11685-11695. doi: 10.1039/d4tb01587h.
The ability of polymeric assemblies to undergo programmable cascades of mesophase transitions is prevalent in many systems in nature, where structural and functional features are tightly bound to maximize activity. In this study, we have examined the ability to program the mesophase transition rates of co-assembled enzyme-responsive polymeric micelles, through fine adjustments of the hydrophobicity of their amphiphilic components. We have utilized the different reactivities of di- and tri-block amphiphiles toward enzymatic degradation as a tool for programming formulations to undergo sequential enzymatically induced transitions from micelles to hydrogels and finally to dissolved polymers. By varying the aliphatic end-groups of PEG-dendron di-block and tri-block amphiphiles, we could demonstrate the remarkable impact of minor modifications to the di-block amphiphiles' structure and hydrophobicity on the transition rates between the different mesophases, ranging from a few hours to a week. Additionally, the study reveals how altering the relative hydrophobicity of its amphiphilic components influences the formulation ratio and enzymatic selectivity, as well as the stability and degradation rate of the resulting hydrogels. The findings underscore the importance of molecular architecture and hydrophobicity as key parameters in the design of programmable enzyme-responsive polymeric assemblies, offering insights into the ability to precisely control multi-step mesophase transitions for tailored functionality.
聚合物组装体能够经历可编程的介相转变级联，这在自然界的许多系统中都很普遍，其中结构和功能特征紧密结合以最大限度地提高活性。在这项研究中，我们通过精细调整其两亲性成分的疏水性，研究了对共组装酶响应聚合物胶束的介相转变速率进行编程的能力。我们利用二嵌段和三嵌段两亲物对酶降解的不同反应性作为一种工具，对制剂进行编程，使其能够依次经历酶诱导的从胶束到水凝胶再到溶解聚合物的转变。通过改变 PEG-树状大分子二嵌段和三嵌段两亲物的脂肪族端基，我们可以证明对二嵌段两亲物结构和疏水性的微小修饰对不同介相之间的转变速率有显著影响，范围从几个小时到一周。此外，该研究揭示了改变其两亲性成分的相对疏水性如何影响制剂比例和酶选择性，以及所得水凝胶的稳定性和降解速率。这些发现强调了分子架构和疏水性作为可编程酶响应聚合物组装体设计的关键参数的重要性，为精确控制多步介相转变以实现定制功能提供了深入了解。
