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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
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Injectable Polymer-Nanoparticle Hydrogels for Local Immune Cell Recruitment
Owen S Fenton, Mark W Tibbitt1, Eric A Appel2
1Macromolecular Engineering Laboratory, Department of Mechanical and Process Engineering , ETH Zürich , Zürich 8092 , Switzerland.
Biomacromolecules
|November 5, 2019
Summary
Researchers developed injectable polymer-nanoparticle hydrogels to recruit immune cells. These novel biomaterials show promise for localized in vivo immunomodulation, enhancing therapies like cancer immunotherapy.
Area of Science:
- Biomaterials Science
- Immunology
- Polymer Chemistry
Background:
- Engineering immune function is crucial for medicine, with successes in vaccines and cancer immunotherapy.
- Developing localized immunomodulatory biomaterials is a key future direction.
- Dendritic cells (DCs) are critical immune cells for initiating adaptive immune responses.
Purpose of the Study:
- To synthesize and characterize shear-thinning and self-healing polymer-nanoparticle (PNP) hydrogels.
- To evaluate the potential of PNP hydrogels as a tunable platform for local dendritic cell (DC) recruitment in vivo.
- To investigate the controlled release of therapeutic proteins from the hydrogel system.
Main Methods:
- Synthesized PNP hydrogels from poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanoparticles with varying PEG brush lengths.
- Assessed hydrogel properties including shear-thinning, self-healing, and protein release kinetics in vitro.
- Loaded hydrogels with CCL21 (a DC-recruiting cytokine) and evaluated DC recruitment in a murine subcutaneous injection model.
Main Results:
- PNP hydrogels demonstrated shear-thinning and self-healing capabilities, with longer PEG brushes enhancing gel formation and recovery.
- Model protein therapeutics were released via Fickian diffusion with minor formulation-dependent variations.
- Subcutaneous injection of CCL21-loaded PNP hydrogels in mice resulted in preferential recruitment of DCs to the injection site.
Conclusions:
- PNP hydrogels represent a simple, tunable, and injectable biomaterial platform for localized immunomodulation.
- This platform facilitates in vivo immune cell programming via minimally invasive subcutaneous delivery.
- The findings support the potential of PNP hydrogels in advancing immunotherapies.
