RESUMEN
Nanodendrite particles (NDs) with densely branched structures and biomimetic architectures have exhibited great promise in tumor therapy owing to their prolonged in vivo circulation time and exceptional photothermal efficiency. Nevertheless, traditional NDs are deficient in terms of specific surface modification and targeting tumors, which restricts their potential for broader clinical applications. Here, we developed coronavirus-like gold NDs through a seed-mediated approach and using silk fibroin (SF) as a capping agent. Our results demonstrate that these NDs have a favorable drug-loading capacity (∼65.25%) and light-triggered release characteristics of doxorubicin hydrochloride (DOX). Additionally, NDs functionalized with specific probes exhibited exceptional surface-enhanced Raman scattering (SERS) characteristics, enabling high-sensitivity Raman imaging of unstained single cells. Moreover, these NDs allowed for real-time monitoring of endocytic NDs for over 24 h. Furthermore, ND@DOX conjugated with tumor-targeting peptides exhibited mild hyperthermia, minimal cytotoxicity, and effective targeting towards cancer cells in vitro, as well as responsiveness to the tumor microenvironment (TME) in vivo. These unique properties led to the highest level of synergistic tumor-killing efficiency when stimulated by a near-infrared (NIR) laser at 808 nm. Therefore, our virus-like ND functionalized with SF presents a novel type of nanocarrier that exhibits significant potential for synergistic applications in precision medicine.
RESUMEN
PURPOSE: Through the method of network pharmacology, the active components and targets of Shenqi Wan (SQW) were excavated, the relationship with novel Coronavirus pneumonia (COVID-19) was discussed, and the possible mechanism of SQW in the treatment of COVID-19 was revealed from the aspects of multicomponents, multitargets, and multipathways. METHODS: Firstly, the active components of SQW were screened from traditional Chinese medicine systems pharmacology database and analysis platform and the 2020 edition of Chinese Pharmacopeia, and the related targets of the components were obtained. Then the disease targets related to COVID-19 were screened from GeneCards and Online Mendelian Inheritance in Man. Venny was used to map the relationship between component-target and disease-target, and String was used to analyze the interaction of common targets. The network was constructed and analyzed by Cytoscape, the function of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) genes was enriched by Metascape, and the molecular docking was verified by CB-Dock. RESULTS: Finally, 45 active components of SQW were obtained, and 72 potential targets were related to COVID-19, angiotensin-converting enzyme 2 (ACE2), interleukin (IL)-6, nitric oxide synthase (NOS3) and, C-reactive protein (CRP),may be the key targets. GO enrichment of 1715 projects, such as lipopolysaccharide stress response, active oxygen metabolism, positive regulation of cell migration, and other GO enrichment. About 136 KEGG pathways, tumor necrosis factor signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor 1-α signaling pathway were obtained. Molecular docking showed that kaempferol, quercetin, luteolin, astragaloside, calyx isoflavone glucoside, matrine, and other COVID-19-related targets such as ACE2, chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), prostaglandin-endoperoxide synthase 2 (PTGS2) have good binding ability. CONCLUSION: According to the above results, it is suggested that SQW may play a role in the treatment of COVID-19 by directly or indirectly combining kaempferol, quercetin, and luteolin with ACE2, 3CLpro, PLpro, and PTGS2 to regulate multiple biological functions and signaling pathways.