Controlled Release in Hydrogels Using DNA Nanotechnology.

Gelatin is a biopolymer widely used to synthesize hydrogels for biomedical applications, such as tissue engineering and bioinks for 3D bioprinting. However, as with other biopolymer-based hydrogels, gelatin-hydrogels do not allow precise temporal control of the biomolecule distribution to mimic biological signals involved in biological mechanisms. Leveraging DNA nanotechnology tools to develop a responsive controlled release system via strand displacement has demonstrated the ability to encode logic process, which would enable a more sophisticated design for controlled release. However, this unique and dynamic system has not yet been incorporated within any hydrogels to create a complete release circuit mechanism that closely resembles the sequential distribution of biomolecules observed in the native environment. Here, we designed and synthesized versatile multi-arm DNA motifs that can be easily conjugated within a gelatin hydrogel via click chemistry to incorporate a strand displacement circuit. After validating the incorporation and showing the increased stability of DNA motifs against degradation once embedded in the hydrogel, we demonstrated the ability of our system to release multiple model cargos with temporal specificity by the addition of the trigger strands specific to each cargo. Additionally, we were able to modulate the rate and quantity of cargo release by tuning the sequence of the trigger strands.

Exploring the influence of Diels-Alder linker length on photothermal molecule release from gold nanorods.

We studied the photothermal release of carboxyfluorescein (CF) linked to the gold surface of gold nanorods (GNRs) by two Diels-Alder adducts of different lengths (n = 4 and n = 9). The functionalized GNRs were irradiated with infrared light to produce photothermal release of CF by a retro-Diels-Alder reaction. The adducts were chemisorbed on the GNRs and the functionalized nanoparticles were characterized by UV-vis, DLS, zeta potential and Raman and surface-enhanced Raman spectroscopy (SERS). On the basis of the degree of nanoparticle functionalization and the SERS results, we inferred the orientation of CF on the surface of the gold nanoparticle. Moreover, we determined the photothermal release profiles of CF from the gold surface by laser irradiation. The release was faster for the longer linker (n = 9). SERS revealed that, for the shorter linker (n = 4), molecules are oriented perpendicularly with respect to the gold surface, thereby maintaining the CF far from the surface. In contrast, the longer linker was observed to be tilted, thus maintaining CF close to the gold surface and therefore potentially favoring the photothermal transfer of energy. These results are relevant for the future development of the spatial and temporal controlled release of drugs by means of gold nanoparticles.

Effects of Polyphosphazene Microspheres Controlled Release of Growth Factors on the Adhesion and Proliferation of Bone Marrow Mesenchymal Stem Cells / 中国运动医学杂志

Objective To investigate the effect of polyphosphazene(PAGP) microspheres controled release of growth factors on the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs).Methods Two kinds of functional poly(alanine ethyl ester-co-glycine ethyl ester) phosphazene microspheres with different ratios of side-substituent groups were synthesized using the emulsion technique.The rate of degradation/hydrolysis of the polymers was carefully tuned to suit the desired application for controlled release.The enzyme-linked immune sorbent assay was utilized to investigate the characterization of the temporal controlled release strategy of microspheres loaded with transforming growth factor-beta 1(TGF-β1) and insulin-like growth factor-l(IGF-1) respectively.The cell adhesion and proliferation stimulated by different growth factors were evaluated by acridine orange staining.Resuits The morphological difference between two PAGP microspheres was identified according to SEM images.The average diameter of two microspheres was 54.22 ± 19.19 μm and 34.11 ± 18.82 μm respectively.The release assay showed that two kinds of microspheres had different release characteristics,with earlier outburst of TGF-β1 and IGF-1 for them to cooperate and later sustained release of TGF-β1 to stimulate the differentiation of stem cells.The result of the acridine orange staining demonstrated that PAGP microspheres supported cell adhesion and growth without obvious cytotoxicity.Meanwhile,the growth factors release strategy significantly improved the proliferation of BMSCs.Conclusion The two polyphosphazene microspheres have a great release-control effect and their controlled release system will have a promising prospect in the future tissue engineering field.

Gold nanoparticles for photothermally controlled drug release.

In this article, we describe how nanoparticles work in photothermally triggered drug delivery, starting with a description of the plasmon resonance and the photothermal effect, and how this is used to release a drug. Then, we describe the four major functionalization strategies and each of their different applications. Finally, we discuss the biodistribution and toxicity of these systems and the necessary requirements for the use of gold nanoparticles for spatially and temporally controlling drug release through the photothermal effect.