The responsiveness of hydrogels to temperature, light, electric/magnetic fields, ultrasound, mechanical forces, pH, redox potentials, and biochemical reagents has been widely used to deliver therapeutic drugs and cells on demand to treat different acute and chronic diseases. In such systems, the controlled release of molecular and cellular payloads is achieved primarily by triggering a transition between the hydrogel and the solution phase or between the hydrogel and the solid state. In order to further promote the application and development of hydrogels, the adjustment of gelatinization through physiological or pathological cues, shape/structure manipulation across multiple length scales, and biocompatible hydrogel formation materials are all directions that need to be considered for optimization in material design.
Recently, Li Xiaodong, a researcher at the School of Medicine of Zhejiang University, professor Zhang Jianxiang of the Army Military Medical University, and others proposed a design and construction strategy for functional hydrogels by responding to the physiological and pathological acidic microenvironment of transformable nanoparticles. These nanoparticles are assembled from a polyvalent hydrophobic, pH-responsive cyclodextrin body material and a polyvalent hydrophilic object macromolecule. Driven by protons, host-guest nanoparticles in pH response can be converted to hydrogels. Therefore, with acid response trigger gelatinization properties, these nanoparticles can act as intelligent nanocarriers for therapeutic agents, enabling triggerable and continuous drug delivery, effectively treating typical inflammatory diseases. The work was published at Advanced Materials under the title "Hydrogel Transformed from Nanoparticles for Prevention of Tissue Injury and Treatment of Inflammatory Diseases."
【Article Highlights】
First, the material design preparation and response to pH transformation behavior
In terms of material design, β-cyclodextrin (β-CD) is used as a functional part of building a polyvalent host molecule called HCD. HCD is formed by combining β-CD with hexachlorocyclotrile (HCTP) by clicking on a chemical reaction. To this end, through the nucleophilic reaction between propynylamine (PA) and HCTP, 6 alkyne units are first introduced into HCTP, and then the β-CD with azide can be clicked between pa-HCTP to produce HCD. On the other hand, the polyvalent guest polymer (8PEG-Ada) is prepared by a condensation reaction between formyl chloride and amine groups to conjugate the Ada moiety to 8-arm polyethylene glycol (8PEG). In order to develop transformable nanoparticles that can form a gel by host-guest complexation when pH is triggered, the study also acetylated HCD to prepare acid-resistant materialSAHCDs. Thus, under non-acidic conditions, AHCDs and 8PEG-Ada can form nanoparticles (AHCPA NPs) by nanoprecipitation and host-guest self-assembly; while under acidic conditions, pH-sensitive nanoparticles can be hydrolyzed to release hydrophilic polyvalent subject molecules that can spontaneously assemble with multivalent guests by enhancing subject-guest interactions to form hydrogels (Figure 1).
Figure 1 Design synthesis of pH-triggered nanoparticles based on subject-object recognition
2. Inflammation treatment
And when administered orally, the transformable nanoparticles can protect the stomach from ethanol or drug-induced damage in mice by forming a hydrogel barrier on the mucous membrane. In addition, these nanoparticles can act as reactive and convertable nanocarriers for various therapeutic agents, enabling triggerable and sustained drug delivery, thereby effectively treating different inflammatory diseases. This nanoparticle conversion hydrogel combines the advantages of nanoparticles and hydrogels, such as good injectability, payload capacity of hydrophobic/hydrophilic drugs and therapeutic cells, excellent stimulation-responsive cargo molecule release performance, and processability required to shape the final structure, and is expected to play a huge role in the treatment of inflammatory diseases.
Figure 2 AHCPA NPs can be converted into hydrogels in the stomach
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Source: Frontiers of Polymer Science