Malignant melanoma, the 19th most prevalent cancer globally, is the primary cause of mortality attributed to cutaneous malignancies. Ginsenoside compound K (CK), a rare ginsenoside renowned for its potent medicinal properties and established safety profile, is widely employed in the treatment and prevention of various diseases. This study aimed to investigate the influence of CK on cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in melanoma, particularly its effects on apoptosis and the immune microenvironment, with the ultimate goal of impeding melanoma growth. In the present study, we used a subcutaneous hormonal tumor model in homozygous mice to investigate whether CK has an inhibitory effect on melanoma growth. The effect of CK on melanoma cell apoptosis was analyzed by flow cytometry, immunohistochemistry, hematoxylin and eosin staining, protein immunoblotting, and RT-qPCR were used to observe the effect of CK on melanoma cytokines. The effects of CK on cGAS-STING pathway in melanoma cells were investigated by protein immunoblotting, immunofluorescence, flow cytometry and molecular docking. The findings demonstrate that CK effectively suppresses melanoma cell proliferation. Molecular docking analysis revealed a binding energy of –6.59 kcal/mol between CK and STING, indicating the potential of CK as a targeted regulator of STING. Mechanistically, CK induces apoptosis in melanoma cells through the Caspase pathway and enhances STING-mediated regulation of the immune microenvironment via the cGAS-STING pathway, thereby inhibiting melanoma growth. Notably, our study provides the first evidence that CK acts as an immune checkpoint agonist, elevating T lymphocyte levels within tumors. CK promotes apoptosis through the Caspase pathway, regulates the cGAS-STING pathway, promotes the production of IFN-β and chemokines by the nucleus, and promotes the infiltration of T-cells in the tumor microenvironment, thus achieving the inhibition of melanoma.
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To address postoperative melanoma issues of high recurrence and poor wound healing, we developed a nanocomposite hydrogel wound patch (MxNd/yCe@M SAC) for cascade sequential therapy. Methotrexate (MTX) loaded Nd/Ce-doped mesoporous bioactive glass was encapsulated in a sulfobetaine-polyacrylamide-carboxymethyl chitosan hydrogel via thermal polymerization. Under the acidic microenvironment of the residual tumor, the amide bonds in MxNd/yCe@M SAC are broken, releasing MxNd/yCe@M. MxNd/yCe@M targets tumor cells, and the combined therapy of mild photothermal treatment and chemotherapy ablates tumor cells. Subsequently, the continuously released MTX down-regulates the expression of pro-inflammatory factors and reshapes the immune microenvironment. Finally, MxNd/yCe@M disintegrates, releasing Si4+, Ca2+, P5+ and Ce3+ ions, which can effectively promote angiogenesis and tissue repair. In the postoperative melanoma model, this method effectively cleared the residual tumors after surgery, shortened the inflammatory period, and promoted tissue regeneration. In conclusion, the nanocomposite hydrogel wound patch for cascade sequential treatment prepared in this study has excellent anti-tumor, immune regulation and tissue repair properties, providing prospective insights for the postoperative treatment of malignant melanoma.
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Breast cancer (BC) is a common malignant tumor in women, which seriously affects the health of patients. In this paper, a plasma nano-composite injectable hydrogel CCT@CAD was developed to realize multi-therapy synergistic anti-cancer. In the acidic tumor microenvironment, CCT@CAD released Au-modified cerium dioxide loaded with cisplatin (CAD), and the surface charge of CAD changed from negative to positive based on the pH-responsive charge inversion characteristic, which significantly improved the internalization efficiency and permeability of tumor cells to CAD. The introduction of Au nanoparticles endowed CAD with localized surface plasmon resonance (LSPR) effects. This effect enhanced electron transfer to activate the Ce active site on the surface of cerium dioxide, thus enhancing the activity of nanozyme, which enabled CAD to rapidly produce O2 and consume glutathione in tumor cells. Meanwhile, Au nanoparticles endowed CAD with excellent photothermal conversion ability, and local hyperthermia could be realized under near infrared laser irradiation. Animal experimental results showed that the tumor inhibition rate was nearly 100% after 14-day treatment of CCT@CAD. The combination of chemotherapy, photothermal therapy and nanozyme therapy proposed in this study provides a new idea for the treatment of BC.
Diabetic wounds, as a complication of diabetes, are slow to heal and seriously affect the quality of life of patients. Functional hydrogel dressing is an effective approach to improve diabetic wound healing. Electrical stimulation (ES) therapy is conducive to promoting cell migration and wound healing. In this work, a multifunctional PPTZ hydrogel wound dressing was developed by freeze-thaw method with polyvinyl alcohol (PVA), phytic acid (PA), tannic acid (TA), and Zinc chloride. The obtained PPTZ hydrogel has good mechanical properties (stress and strain of 700.03 kPa and 575.08%), light transmittance (close to 100%) and antibacterial rate (over 75%). With good biocompatibility, antioxidant abilities and conductivity, the PPTZ hydrogel could effectively promote the healing of diabetic wounds with two weeks under the action of electric field, which provides an auxiliary treatment strategy for diabetic patients.
Burns are a common medical problem globally, and wound infection is one of the major causes of inducing related complications. Although antibiotics effectively prevent wound infections, the misuse of antibiotics has created a new problem of superbugs. Herein, we propose a new strategy to obtain pH-responsive antimicrobial P-ZIF (ZIF: zeolitic imidazolate framework) by loading polyhexamethylenebiguanide (PHMB) into the framework of ZIF-8 nanoparticles. This will enable PHMB to be released in the weak acid environment of an infected wound. To address burn infections, P-ZIF nanoparticles were loaded into a hydrogel system made of sodium alginate (SA) and 3-aminophenylboronic acid modified human-like collagen (H-A) through borate ester bonds. The resulting H-A/SA/P-ZIF (HASPZ) hydrogel dressing not only possesses antibacterial and wound healing properties but also has dual pH responsiveness to prevent the overuse of medication while effectively treat deep second-degree burns. Therefore, P-ZIF nanoparticles and the corresponding HASPZ hydrogel dressing are considered of significant importance in antimicrobial, drug delivery, and wound repair.
The repair and treatment of tumor bone defects is a difficult problem to solve urgently in clinical medicine. After tumor resection, patients are not only faced with a large area of bone defect, but also may have the risk of tumor recurrence, which can easily cause huge physical and mental harm to patients. In this study, we successfully designed and constructed an organic/inorganic composite microgel bone powder (S-H-M3%Ce/3%Se) based on cerium (Ce) and selenium (Se) elements co-doped mesoporous bioactive glass (M3%Ce/3%Se), sodium alginate (SA), and recombinant human-like collagen (HLC). The obtained S-H-M3%Ce/3%Se could inhibit the growth of osteoma cells and promote the growth of normal cells, and effectively promote the repair of defect bone. The integration of the “treatment and repair” organic/inorganic composite microgel bone powder provided a new strategy for the treatment of cancerous bone defects.
Solar dermatitis is an acute or chronic high incidence of skin injury caused by ultraviolet (UV) radiation based on strong sunlight, which seriously endangers people's health. In this study, we designed and demonstrated enzyme-catalyzed semi-inter penetrating polymer network (Semi-IPN) sprayable nanodrug-loaded hydrogels based on gelatin, 3-(4-hydroxyphenyl) propionic acid (HPA), polyvinyl alcohol (PVA), glycerol, and dexamethasone sodium phosphate (DEXP) for solar dermatitis. The hydrogels had high water content, excellent biocompatibility, effective encapsulation and sustained release of nanodrugs, anti-inflammatory, and strong anti-ultraviolet B (anti-UVB) radiation properties based on glycerol and phenol functional groups, but also controllable spray gelation mode to make them adhere well on the dynamic skin surfaces and achieve continuous transdermal drugs delivery for solar dermatitis. The sprayable nanodrug-loaded hydrogel systems could be used as a highly effective therapeutic method for solar dermatitis, and also provide a good strategy for designing novel nanodrug-loaded hydrogel delivery systems.
Whitlockite (WH, Ca18Mg2(HPO4)2(PO4)12) is an important inorganic phase in human bones and has positive significance for participating in the bone reconstruction process. In this paper, we report different doping strategies to prepare WH and WH-Ln (Eu/Tb) nanocrystals, and have successfully synthesized WH-Ln (Eu/Tb) nanoparticles (NPs) with bright red or green fluorescence based on ions exchange doping by two-step hydrothermal reaction. WH-5%Ln (Eu/Tb) NPs with the best fluorescence properties were successfully applied to live cell imaging, and WH-5%Eu NPs were implanted into the bone defect site in rabbit femoral condyles to visually observe its degradation process. The related results would help us understand WH nanocrystals and further expand their potential applications in tissue engineering and related fields.
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