A hybrid particle-hydrogel composite for oligonucleotide-mediated pulsatile protein release

The development of pulsatile protein delivery systems is challenging and can advance the treatment of various human diseases. Herein, we introduce a novel composite as the delivery system using nucleic aptamers to retain and release target proteins at will. The composite was composed of affinity particles embedded in a hydrogel network where the affinity particles were functionalized with the aptamers. Not only did the aptamers function as binding sites for proteins in the composite, but also as triggering sites for the pulsatile release of proteins. To demonstrate this idea, platelet-derived growth factor-BB, its aptamer, and agarose hydrogel were used as the model. Microscopy imaging revealed that the particles were well distributed in the composite. The measured storage and loss moduli did not differ significantly in comparison of the composite with the native agarose gel, indicating that the incorporated particles did not alter the mechanical properties of the material. The release experiment showed that the protein release rate in the aptamer-incorporated composite dramatically decreased in normal conditions as compared to the control composite due to the high binding affinity of the aptamers. After being triggered by complementary oligonucleotides, the system could release the bound proteins in a pulsatile manner at predetermined time points.