Introduction: Stimuli-responsive hydrogels have attracted considerable attention as smart biomaterials because of their many future opportunities in biomedical fields. However, very few studies on biologically stimuli-responsive hydrogels that undergo changes in the volume in response to a target biomolecule, i.e., biomolecule-responsive hydrogels, have been undertaken in spite of their many potential applications to drug delivery systems and molecular diagnostics. We proposed a novel strategy for designing biomolecule-responsive hydrogels, which utilizes biomolecular complexes as dynamic crosslinks that dissociate and associate in response to a target biomolecule[1]. For example, the bioconjugated hydrogels with antigen-antibody and lectin-glycopolymer complex crosslinks exhibited unique biomolecule-responsive swelling/shrinking changes[2]-[5]. This paper describes target biomolecule-responsive hydrogels that undergo changes in the volume in response to target DNA or two antigens.
Materials and Methods: Bioconjugated hydrogels with DNA duplex crosslinks (DNA-crosslinked hydrogels) were prepared by the copolymerization of the DNA duplexes with acryloyl groups, acrylamide (AAm) and N, N'-methylenebisacrylamide (MBAA) using redox initiator.
Bioconjugated hydrogels with two antigen-antibody complex crosslinks were designed using rabbit γ-immunoglobulin G (IgG), bovine serum albumin (BSA) and their antibodies (goat anti-rabbit IgG, anti-BSA). As first networks, bioconjugated hydrogels with the IgG antigen-antibody complexes were prepared by copolymerization of the antigen-antibody complexes with acryloyl groups, AAm and MBAA using redox initiators. Then the second networks with BSA antigen-antibody complexes were formed by the similar copolymerization within the first networks to obtain bioconjugated hydrogels having an interpenetrating polymer network (IPN) structure with two antigen-antibody complex crosslinks (IgG-BSA IPN hydrogels).
Results and Discussion: The swelling ratio of DNA-crosslinked hydrogels strongly depended on the base sequence of single-stranded (ss) DNA (Fig. 1). The investigations into the crosslinking density revealed that their DNA-responsive swelling was attributed to a decrease in their crosslinking density, which was caused by the dissociation of the DNA duplex crosslinks, in the presence of target ssDNA.
The swelling ratio of IgG-BSA IPN hydrogels increased more highly in a buffer solution with both IgG and BSA than in a solution with either IgG or BSA alone (Fig. 2). The multiple antigens-responsive swelling of the IPN hydrogels was caused by dissociation of both IgG and BSA antigen-antibody complex crosslinks in the presence of both IgG and BSA. Furthermore, the IPN hydrogels regulated the permeation of a model drug in response to both IgG and BSA.
Conclusion: Bioconjugated hydrogels that underwent changes in the volume in response to target DNA and two proteins were strategically designed using biomolecular complex crosslinks. Such biomolecule-responsive hydrogels have many potential applications as smart biomaterials for self-regulated DDS and biomolecular diagnosis.
References:
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