[Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

[Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review].

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

[Mechanism of Linderae Radix against gastric cancer based on network pharmacology and in vitro experimental validation].

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.

Network Pharmacology Analysis, Molecular Docking, and In Vitro Verification Reveal the Action Mechanism of Prunella vulgaris L. in Treating Breast Cancer.

Background: Prunella vulgaris L. is effective in the treatment of breast cancer (BRCA); however, the underlying mechanism is still unclear. The aim of this study was to elucidate the mechanism of treatment of BRCA by P. vulgaris using network pharmacology and molecular docking technology, and to verify the experimental results using human BRCA MDA-MB-231 cells. Methods: Active components and action targets of P. vulgaris were determined using the TCMSP™, SwissTarget Prediction™, and TargetNet™ databases. GeneCards™ and OMIM™ provided BRCA targets. After obtaining common targets, a protein-protein interaction (PPI) network was constructed using the STRING™ database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the Xiantao™ academic database. Cytoscape™ was used to construct "single drug-disease-component-target" and "single drug-disease-component-target-pathway" networks. The Human Protein Atlas™ was used to determine protein expression levels in BRCA cell lines. AutoDock tools™ were used to carry out molecular docking for the first 10 targets of quercetin and the PPI network. Finally, the abovementioned results were verified using cell experiments. Results: We obtained 11 active components, 198 targets, and 179 common targets, including DUOX2, MET, TOP2A, and ERBB3. The results of KEGG pathway analysis screened 188 related signaling pathways and indicated the potential key role of PI3K-Akt and MAPK signaling pathways in the antibreast cancer process of P. vulgaris. The results of molecular docking showed that the first 10 targets of quercetin interacted well with the protein network. Cell experiments showed that quercetin effectively inhibited the proliferation of MDA-MB-231 cells by regulating apoptosis and cell cycle, which may be partly related to the MAPK signaling pathway. Conclusion: Synergistic effects of multiple components, targets, and pathways on the anti-BRCA activity of P. vulgaris could provide a theoretical basis for further study on its complex anti-BRCA mechanism.

Water-Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR-II Photothermal Anti-Bacterial Therapy.

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.

Luminescent, Oxygen-Supplying, Hemoglobin-Linked Conjugated Polymer Nanoparticles for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising method for cancer treatment. Two parameters that influence the efficacy of PDT are the light source and oxygen supply. Herein, we prepared a system for PDT using hemoglobin (Hb)-linked conjugated polymer nanoparticles (CPNs), which can luminesce and supply oxygen. Hb catalyzes the activation of luminol, the conjugated polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) nanoparticles can absorb the chemiluminescence of luminol through chemiluminescence resonance energy transfer (CRET) and then sensitize the oxygen supplied by Hb to produce reactive oxygen species that kill cancer cells. This system could be used for the controlled release of an anticancer prodrug. The system does not need an external light source and circumvents the insufficient level molecular oxygen under hypoxia. This work provides a proof-of-concept to explore smart and multifunctional nanoplatforms for phototherapy.

Photothermal-Responsive Conjugated Polymer Nanoparticles for Remote Control of Gene Expression in Living Cells.

Remote control and noninvasive manipulation of cellular bioprocess has received intensive attention as a powerful technology to control cell functions. Here, a strategy is developed to remotely control intracellular gene expression with high spatial and temporal resolutions by using photothermal-responsive conjugated polymer nanoparticles (CPNs) as the transducer under near-infrared light irradiation. After being modified with positive charged peptide, the CPNs with superior photothermal conversion capacity could effectively coat on the surface of living cells and generate localized heat to trigger target gene expression. The heat-inducible heat shock protein-70 promoter starts transcription of downstream EGFP gene in response to heat shock, thus producing green fluorescent protein in the living cells. The combination of heat-inducible gene promoter and photothermal-responsive CPNs provides a method for the development of thermogenetics.

Supramolecular Radical Anions Triggered by Bacteria In†Situ for Selective Photothermal Therapy.

A supramolecular complex that can be selectively reduced to radical anions in situ by facultative anaerobic bacteria is reported. To this end, a water-soluble bifunctional monomer bearing perylene diimide was synthesized, and its supramolecular complex with cucurbit[7]uril was fabricated on the basis of host-guest complexation, which could be reduced to forming radical anions in the presence of E. coli. It was found that this supramolecular complex could display different ability of generating radical anions by facultative anaerobic and aerobic bacteria in terms of their various reductive abilities. The selective antibacterial activity of the supramolecular complex could be realized by the photothermal performance of the radical anions under near-infrared irradiation. It is anticipated that this method may lead to a novel bacteria-responsive photothermal therapy to regulate balance of bacterial flora.