Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently, there are limited approaches to tailor 3D scaffolds cross-linked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-cross-linking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely, an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior cross-linking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of cross-linking at different pH values is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogel demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase-mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product rendered the tissue-adhesive properties by bonding two bone tissues. The aldehyde functionality also facilitated facile post-synthetic modifications with nucleophilic reagents. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3-6 days of study.
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PMID:First Aldol Cross-Linked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Hydrogel with Tissue Adhesive Properties. 3155 Aug 78

The antitumor efficacy of tumor vaccines is often limited by weak T cell responses and poor activated T cells infiltration. Herein, we reported a novel synergistic strategy to simultaneously overcome these two obstacles to realize enhanced tumor elimination. To induce the robust T cell responses, we designed a minimalist tumor nanovaccine based on stepwise electrostatic interactions. The dual-functional delivery system PEI/CaCO3 (polyethylenimine coated CaCO3), could not only act as a vaccine carrier that absorbed antigen ovalbumin (OVA) and adjuvant unmethylated cytosine-phosphate-guanine (CpG) with high efficiency, but also work as an underlying adjuvant to activate bone marrow-derived dendritic cells (BMDCs). Therefore, the formed PEI/CaCO3/OVA/CpG vaccines (NVs) realized the significant enhancement of both the BMDCs activation and the specific responses of T cells in vivo. In addition, to enhance the infiltration of activated T cells in the tumor sites, the Spam1 gene, which could express hyaluronidase (HAase), was explored using PEI as the gene carrier shielded with aldehyde modified polyethylene glycol (CHO-PEG-CHO) through pH responsive Schiff base bonds. PEG/PEI/pSpam1 (pSpam1@NPs) could achieve a high HAase expression in the tumor sites to further degrade the tumor extracellular matrix, thus promoting the infiltration of immune cells. Besides, the degradation of extracellular matrix increased blood perfusion and relieved the tumor hypoxia to modulate the immune-suppressive microenvironment. Highly enhanced antitumor efficiency and tumor re-challenge prevention were achieved by combined NVs with pSpam1@NPs in B16-OVA bearing mice. The facile synergistic strategy we presented here is expected to be further used for personalized immunotherapy in the future.
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PMID:Synergistic tumor immunological strategy by combining tumor nanovaccine with gene-mediated extracellular matrix scavenger. 3242 91


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