Potential of the nanoplatform and PROTAC interface to achieve targeted protein degradation through the Ubiquitin-Proteasome system.

In eukaryotic cells, the ubiquitin-proteasome system (UPS) plays a crucial role in selectively breaking down specific proteins. The ability of the UPS to target proteins effectively and expedite their removal has significantly contributed to the evolution of UPS-based targeted protein degradation (TPD) strategies. In particular, proteolysis targeting chimeras (PROTACs) are an immensely promising tool due to their high efficiency, extensive target range, and negligible drug resistance. This breakthrough has overcome the limitations posed by traditionally "non-druggable" proteins. However, their high molecular weight and constrained solubility impede the delivery of PROTACs. Fortunately, the field of nanomedicine has experienced significant growth, enabling the delivery of PROTACs through nanoscale drug-delivery systems, which effectively improves the stability, solubility, drug distribution, tissue-specific accumulation, and stimulus-responsive release of PROTACs. This article reviews the mechanism of action attributed to PROTACs and their potential implications for clinical applications. Moreover, we present strategies involving nanoplatforms for the effective delivery of PROTACs and evaluate recent advances in targeting nanoplatforms to the UPS. Ultimately, an assessment is conducted to determine the feasibility of utilizing PROTACs and nanoplatforms for UPS-based TPD. The primary aim of this review is to provide innovative, reliable solutions to overcome the current challenges obstructing the effective use of PROTACs in the management of cancer, neurodegenerative diseases, and metabolic syndrome. Therefore, this is a promising technology for improving the treatment status of major diseases.

An epigallocatechin gallate-amorphous calcium phosphate nanocomposite for caries prevention and demineralized enamel restoration.

Biomineralization with amorphous calcium phosphate (ACP) is a highly effective strategy for caries prevention and defect restoration. The identification and interruption of cariogenic biofilm formation during remineralization remains a challenge in current practice. In this study, an epigallocatechin gallate (EGCG)-ACP functional nanocomposite was developed to prevent and restore demineralization by integrating the antibacterial property of EGCG and the remineralization effect of ACP. The synthesized EGCG-ACP showed good biocompatibility with L-929 â€‹cells and human gingival fibroblasts. Under neutral conditions, the sustained release of ACP from EGCG-ACP restored the microstructure and mechanical properties of demineralized enamel. Under acidic conditions, protonated EGCG released from EGCG-ACP exerted a strong antibacterial effect, and the ACP release rate doubled within 4 â€‹h, resulting in the prevention of demineralization in the presence of cariogenic bacteria. The pH-responsive features of EGCG-ACP to promote the protonation of EGCG and ACP release facilitated its performance in remineralization effect to overcome the difficulty of restoring demineralized enamel in a cariogenic acidic environment, which was evidenced by the in vivo experiment carried out in a rat oral cariogenic environment. The results of this study indicate the potential of EGCG-ACP for the prevention of enamel demineralization and provide a theoretical basis its application in populations with high caries risk.

The design, construction and application of graphene family composite nanocoating on dental metal surface.

Enhancement of the biological and mechanical properties of dental metals is important for accommodation with therapeutic schemes in different stomatological disciplines. Nanocoatings based on graphene family nanomaterials (GFNs) improve the topological structure and physicochemical properties of metal surfaces, endowing them with new properties while maintaining inherent mechanical properties. Nano-composite coatings, composed of GFNs with one or more type of polymer, metal, oxide, and inorganic nonmetallic compound, offer more matching modification schemes to meet multifunctional oral treatment requirements (e.g., anti-bacterial and anti-corrosive activity, osteogenesis and angiogenesis). This review describes recent progress in the development of GFN composite nanocoatings for the modification of dental metals, focus on biological effects in clinical settings. Underlying molecular mechanisms, critical modification schemes, and technical innovation in preparation methods are also discussed. The key parameters of GFN composite nanocoating surface modification are summarized according to effects on cellular responses and antibacterial activity. This review provides a theoretical reference for the optimization of the biological effects and application of GFN composite nanocoatings for dental metals, and the promotion of the environmentally friendly large-scale production of high-quality multifunctional GFN-based nanocoatings in the field of oral science.

Biological Effects, Applications and Design Strategies of Medical Polyurethanes Modified by Nanomaterials.

Polyurethane (PU) has wide application and popularity as medical apparatus due to its unique structural properties relationship. However, there are still some problems with medical PUs, such as a lack of functionality, insufficient long-term implantation safety, undesired stability, etc. With the rapid development of nanotechnology, the nanomodification of medical PU provides new solutions to these clinical problems. The introduction of nanomaterials could optimize the biocompatibility, antibacterial effect, mechanical strength, and degradation of PUs via blending or surface modification, therefore expanding the application range of medical PUs. This review summarizes the current applications of nano-modified medical PUs in diverse fields. Furthermore, the underlying mechanisms in efficiency optimization are analyzed in terms of the enhanced biological and mechanical properties critical for medical use. We also conclude the preparation schemes and related parameters of nano-modified medical PUs, with discussions about the limitations and prospects. This review indicates the current status of nano-modified medical PUs and contributes to inspiring novel and appropriate designing of PUs for desired clinical requirements.