Chunhua Ren

When Molecular Probes Meet Self‐Assembly: An Enhanced Quenching Effect

We demonstrate that the incorporation of one or two amino acids of phenylalanine (F) or 4-fluoro phenylalanine ((f)F) will greatly lower the background fluorescence intensities of conventional quenched probes with quenchers. This enhanced quenching effect was due to the synergetic effect of the aggregation caused quenching and the presence of a quencher. Such strategy will not greatly affect the enzyme recognition properties to the probes. We also demonstrated that our self-assembled nanoprobe with the enhanced quenching effect showed a better performance in cells for the detection of cell apoptosis than the unassembled probes. Our study demonstrates that using molecular self-assembly can optimize and improve the performance of molecular probes and it provides a simple but very useful strategy to boost the signal-to-noise ratios of fluorescence probes.

Enzyme-triggered self-assembly of a small molecule: a supramolecular hydrogel with leaf-like structures and an ultra-low minimum gelation concentration

We report on the use of a phosphatase to assist the formation of leaf-like structures and a supramolecular hydrogel with an ultra-low minimum gelation concentration. The compound can gel water at a minimum gelation concentration of 0.01 wt%, which is the lowest gelation concentration reported up to now. The images obtained by transmission electron microscopy (TEM) reveal the existence of leaf-like structures serving as the matrix of the hydrogels. The stability of the hydrogels was studied and emission spectra were used to get information about the molecular packing in the leaf-like structures. Since lowering the concentration of the gelator decreases the toxicity of the resulting hydrogels, ultra-low concentration gels have potential uses as biocompatible biomaterials for, e.g., cell cultures, tissue engineering, and drug delivery.

A saccharide-based supramolecular hydrogel for cell culture

It is well known that the saccharides forming the intricate sugar coat that surrounds the cells play important biological roles in intercellular communication and cell differentiation. Therefore, it is worthwhile developing saccharide-based hydrogels for cell culture study. In this study, three novel saccharide-based compounds were designed and synthesized. It was found that one of them could form hydrogels efficiently, while the other two precipitated from water. The stability of the resulting hydrogel was tested, and the supramolecular nanofiber with fiber diameters in the range of 80-300nm was characterized as the structural element by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fluorescence microscopy revealed that extensive hydrogen bonds between sugar rings assisted the formation of efficient π-π stacking between aromatic naphthalene groups, thus resulting in the formation of a stable hydrogel in aqueous solution. When the gel was applied for mouse embryonic fibroblast (NIH 3T3), human hepatocellular carcinoma (HepG2), AD293 and HeLa cells culture in two dimensional environments, all of them showed a very good adhesion and good proliferation rate on the top of the hydrogel. These results indicates that the biocompatible hydrogel reported here has a potential to be developed into useful materials for in vitro cell culture, drug delivery, and tissue engineering.

Using a mild hydrogelation process to confer stable hybrid hydrogels for enzyme immobilization

In addition to the widely used polymeric hydrogels, molecular hydrogels are also emerging as promising biomaterials. However, molecular hydrogels typically suffer from poor mechanical properties and relatively low in vivo stability. Here we report on the preparation of two hybrid hydrogels (Hgel I and Hgel II) by the combination of two molecular hydrogelators and alginate, respectively. First, the molecular hydrogelator and sodium alginate were dissolved in water, and then a hydrogel was formed upon triggering by enzymes or reductants. Afterward the resulting hydrogel was soaked in calcium ion solution to form the hybrid hydrogel. The preparation process was easy and mild which allowed the resulting hybrid hydrogels to act as carriers for biomacromolecules such as enzymes. Both Hgel I and Hgel II had better stabilities and mechanical properties than the calcium alginate gel (CAgel) alone. Hgel I had exceptional stability compared with Hgel II and CAgel. The reason we propose is that molecular hydrogelators in Hgel I interacted with alginate more strongly than molecular hydrogelators in Hgel II according to the fluorescence results of these gels. Unlike the porous microstructure of molecular hydrogels, the microstructure of two hybrid hydrogels was almost the same as that of CAgel (film-like morphology) except with some nanofibers embedded. We found that Hgel I was an ideal carrier for enzyme immobilization with high recyclable properties and excellent preservation of enzyme activities due to its good mechanical strength. However, Hgel II was not suitable as a carrier for immobilized lactase probably due to poor affinity between Hgel II and the substrate. Combining the advantages of molecular hydrogels and polymeric hydrogels would broaden the applications of both kinds of hydrogels in the future.

A supramolecular hydrogel for the delivery of bortezomib

Here we reported on a supramolecular hydrogel for the delivery of an anti-cancer drug bortezomib.

Nanospheres of doxorubicin as cross-linkers for a supramolecular hydrogelation

In this study, we synthesized a peptide of Nap-GFFYGRGD, which could self-assemble into supramolecular nanofibers. The peptide itself could only form nanofibers but not hydrogels due to the relative weak inter-fiber interactions. The resulting nanofibers were then utilized as the vehicles for anticancer drug doxorubicin. It was found that the nanofibers of Nap-GFFYGRGD could not encapsulate doxorubicin, whereas the drug formed nanospheres, which were located at the surface of the nanofibers. Due to the electrostatic interactions between the negatively charged nanofibers and the positively charged doxorubicin nanospheres, the doxorubicin nanospheres were able to serve as a cross-linker to increase the inter-fiber interactions, leading to the formation of stable three-dimentional fiber networks and hydrogels. The resulting doxorubicin-peptide hydrogels were capable of releasing the drug in a sustained manner, which also showed comparable cytotoxicity as compared to free doxorubicin against a variety of cancer cell lines including HeLa and MCF-7 cancer cells. Therefore, this successful example using drug as the peptide nanofiber cross-linkers provided a new strategy for fabricating supramolecular hydrogelation for controlled delivery of anticancer drugs.

A releasable disulfide carbonate linker for molecular hydrogelations

We used a releasable disulfide carbonate linker to construct precursors of gelators and form stable gels.

Redox-controllable self-assembly and anti-bacterial activity of a vancomycin derivative

We report a selenium containing vancomycin derivative with redox-controllable self-assembly property and anti-bacterial activity.