Injectable Diels–Alder cycloaddition hydrogels with tuneable gelation, stiffness and degradation for the sustained release of T-lymphocytes

Abstract

Highly efficient, selective and cytocompatible fulvene–maleimide cycloaddition chemistry was applied for the preparation of injectable, cell encapsulating/releasing hydrogels with tuneable gelation and degradation kinetics.

Exploring the versatility of pentafulvene–maleimide cycloaddition as a ligation strategy: buffer and pH effects

“…23 DAC was reported to proceed efficiently in a tetrahydrofuran : water (2 : 1 v/v) mixture to afford 7-alkylidene norborn-2-ene cycloadducts that were stable to retro-Diels Alder reactions and enzymatic degradation in the presence of PBS ( pH 7.4) and human blood plasma over 24 h, respectively. Detailed kinetic studies of the [4 + 2] cycloaddition between 6,6-dimethyl pentafulvenes and maleimide derivatives in PBS (10 mM, pH 7.4) to afford 7-alkylidene norborn-2-ene cycloadducts were previously reported by our group, 24 including cross-reactivity studies of pentafulvenes with a range of functional groups and pentafulvene stability between pH 6-9 over 48 h. In addition, we have also reported the stability of 7-alkylidene norborn-2-ene cycloadducts in aqueous solutions without any evidence for hydrolysis or retro-Diels Alder reactions over at least 24 h. 24 The broadening applications of the pentafulvene-maleimide ligation has been demonstrated for the preparation of hydrogels for cell encapsulation 25,26 and for generating mass spectrometry-cleavable labels (mass tags) for mass spectrometric detection of biomolecules. 27 To further investigate the potential of the pentafulvene-maleimide ligation for different bioconjugation applications, we herein report the stability of the pentafulvene 1 and maleimide 2 reactant partners as a model system in different buffer systems and the rate, efficiency and stereoselectivity of their cycloaddition reaction (Scheme 2).…”

Application of Hydrogels as Carrier in Tumor Therapy: A Review

“… The hydrogels based on different monomers. (a) Synthesis of PEG derivatives (PEG x ‐Mal 2 and PEG 10k ‐Ful 4 ) hydrogels [14] . Copyright (2022), Royal Society of Chemistry.…”

“…The effects of antitumor drugs and sustained cells release were achieved by regulating the degradation of PEG‐based hydrogels. Yan et al [14] . prepared a PEG hydrogel with tunable properties.…”

“…The effects of antitumor drugs and sustained cells release were achieved by regulating the degradation of PEG-based hydrogels. Yan et al [14] prepared a PEG hydrogel with tunable properties. Encapsulation and release of tumor-treating T cells were achieved by adjusting the degradation time of the hydrogel.…”

“…The modification of steroid drugs can improve the targeting effect and bioavailability, but sustained release of the drug for a long time will be a noteworthy problem. [14] Copyright (2022), Royal Society of Chemistry. (b) Structural of carboxymethyl chitosan-based double-crosslinked hydrogels.…”