Self-Immolative Hydrogels with Stimulus-Mediated On–Off Degradation

Abstract

Hydrogels are of interest for a wide range of applications from sensors to drug delivery and tissue engineering. Self-immolative polymers, which depolymerize from end-to-end following a single backbone or end-cap cleavage, offer advantages such as amplification of the stimulus-mediated cleavage event through a cascade degradation process. It is also possible to change the active stimulus by changing only a single end-cap or linker unit. However, there are very few examples of self-immolative polymer hydrogels, and the reported examples exhibited relatively poor stability in their nontriggered state or slow degradation after triggering. Described here is the preparation of hydrogels composed of self-immolative poly(ethyl glyoxylate) (PEtG) and poly(ethylene glycol) (PEG). Hydrogels formed from 2 kg/mol 4-arm PEG and 1.2 kg/mol PEtG with a light-responsive linker end-cap had high gel content (90%), an equilibrium water content of 89%, and a compressive modulus of 26 kPa. The hydrogel degradation could be turned on and off repeatedly through alternating cycles of irradiation and dark storage. Similar cycles could also be used to control the release of the anti-inflammatory drug celecoxib. These results demonstrate the potential for self-immolative hydrogels to afford a high degree of control over responses to stimuli in the context of smart materials for a variety of applications.

Recent Advances in Stimuli-Responsive Self-Immolative Polymers for Drug Delivery and Molecular Imaging

“…Recently, researchers from the same group prepared hydrogels of four-armed polyethylene glycol cross-linked by PEtG with different chain lengths (Figure 9A). 107 After UV light irradiation, the hydrogel quickly responded to the stimulus and could open or close the gel's degradation depending on the presence of the stimulus. They further evaluated its potential for controlling drug release using celecoxib (CXB) as a model drug and the results showed that drug release was significantly enhanced after UV light irradiation, with an accumulated release rate of CXB reaching ∼80%.…”

“…This phenomenon may be attributed to two factors: first, the degradation of the second-generation dendritic SIP itself requires a longer time than the first generation; and second, the second-generation dendritic SIPs provide more cross-linking sites that result in a denser cross-linking network. Recently, researchers from the same group prepared hydrogels of four-armed polyethylene glycol cross-linked by PEtG with different chain lengths (Figure A) . After UV light irradiation, the hydrogel quickly responded to the stimulus and could open or close the gel’s degradation depending on the presence of the stimulus.…”

“…Schematic diagram showing the smart hydrogels with a SIP-based cross-linker (A) and a SIP-based backbone (B). (A) Reproduced with permission from reference . Copyright 2024 American Chemical Society.…”

Emerging Trends in the Chemistry of End-to-End Depolymerization

“…Two different generations of dendrons with alkyne moieties at their peripheries were cross-linked with 4-arm PEG-azides via CuAAC, leading to self-immolative hydrogels with distinct physical and degradation properties. Very recently, we further constructed self-immolative hydrogels from phototriggered depolymerizable poly­(ethyl glyoxylate) and 4-arm PEG-azides via CuAAC . The hydrogel degradation could be turned on and off repeatedly through alternating cycles of UV irradiation and dark storage.…”

“…Very recently, we further constructed self-immolative hydrogels from phototriggered depolymerizable poly(ethyl glyoxylate) and 4-arm PEG-azides via CuAAC. 140 The hydrogel degradation could be turned on and off repeatedly through alternating cycles of UV irradiation and dark storage. Similar cycles could also be used to control the release of the physically encapsulated anti-inflammatory drug celecoxib.…”