The field of polymer mechanochemistry has experienced rapid growth over the past decade, propelled largely by the development of force-activated functional groups (mechanophores) and polymer structure-reactivity principles for mechanochemical transduction. In addition to fundamental guidelines for converting mechanical input into chemical output, there has also been increasing focus toward the application of polymer mechanochemistry for specific functions, materials, and devices. These endeavors are made possible by multidisciplinary approaches involving designer polymer synthesis, computational modeling and design, and different fields of engineering. Described herein are contributions from our group on the development of flex activated mechanophores for small molecule release and star polymer mechanochemistry, as well as collaborative efforts toward mechanochemically triggered depolymerizations and 3D printed mechanochromic materials.
Functional and Responsive Materials
Sunflower Polymers for Folate-Mediated Drug Delivery
Polymeric delivery vehicles can improve the safety and efficacy of chemotherapy drugs by facilitating preferential tumor delivery. Polymer–drug conjugates are especially attractive carriers because additional formulation steps are not required during manufacturing, and drug release profiles can be altered based on linker choice. For clinical translation, these vehicles should also be reproducibly and controllably synthesized. Recently, we reported the development of a class of materials called “sunflower polymers,” synthesized by controlled radical polymerization of hydrophilic “petals” from a cyclic multimacroinitiator “core”. This synthesis strategy afforded control over the size of the polymer nanostructures based on their petal polymerization time. In this work, we demonstrate that particle size can be further tuned by varying the degree of polymerization of the cyclic core in addition to that of the petals. Additionally, we investigate the application of these materials for tumor-targeted drug delivery. We demonstrate that folate-targeted, doxorubicin-conjugated sunflower polymers undergo receptor-mediated uptake into cancer cells and pH-triggered drug release leading to cytotoxicity. These materials are attractive as drug carriers due to their discrete and small size, shielded drug cargo that can be triggered for release, and relative ease of synthesis.
Additive Manufacturing of Mechanochromic Polycaprolactone on Entry-Level Systems
This paper aims to explore and demonstrate the ability to integrate entry-level additive manufacturing (AM) techniques with responsive polymers capable of mechanical to chemical energy transduction. This integration signifies the merger of AM and smart materials.
ATRP Synthesis of Sunflower Polymers Using Cyclic Multimacroinitiators
Polymers with advanced architectures can now be readily and reproducibly synthesized using controlled living polymerization. These materials are attractive as potential drug carriers due to their tunable size, versatile methods of drug incorporation and release, and ease of functionalization with targeting ligands. In this work, we report the design and development of macrocyclic brush or “sunflower” polymers, synthesized by controlled radical polymerization of hydrophilic “petals” from a cyclic multimacroinitiator “core”. These nanostructures can be synthesized with low polydispersity and controlled sizes depending on polymerization time. We further demonstrate that folate-functionalized sunflower polymers facilitate receptor-mediated uptake into cancer cells. These materials therefore show potential as drug carriers for anticancer therapies.
1,2-Oxazine Linker as a Thermal Trigger for Self-Immolative Polymers
We have demonstrated the site-specific thermal activation of self-immolative polymers (SIPs) using a bicyclic oxazine as a temperature-sensitive triggering moiety. The oxazine-based trigger was installed at the junction of a SIP-poly(N,N-dimethylacrylamide) (PDMA) diblock copolymer via oxidation of hydroxyurea end groups on the SIP and in situ [4 + 2] cycloaddition with cyclopentadiene-functionalized PDMA. The trigger undergoes a thermally-driven cycloreversion which ultimately leads to initiation of the depolymerization process. The temperature dependence of activation and depolymerization were investigated, along with the mechanism of activation. The relative rates of depolymerization at different temperatures suggested to us that the thermal trigger design may be a good candidate for on-demand activation of SIPs with minimal background triggering.
Controlled Depolymerization: Stimuli-Responsive Self-Immolative Polymers
Self-immolative polymers (SIPs) are unique macromolecules that are able to react to multiple types of environmental influences by giving amplified response outputs. When triggering moieties installed at SIP chain ends are activated by their corresponding stimuli, a spontaneous head-to-tail depolymerization ensues, often involving multitopic release of small molecules. SIP designs have evolved a high degree of modularity in each of their functional components, enabling a broad range of utility and applications-driven tuning. In this Perspective, we summarize and discuss recent progress in this nascent area of research, including (i) synthesis of different types of SIPs, (ii) design and evaluation of triggering moieties, (iii) depolymerization mechanisms and kinetics, (iv) applications of SIPs, and (v) outlook and challenges facing the field.