Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer.

Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264.7 (RAW) membranes, creating a hybrid biomimetic coating referred to as TRM. Subsequently, we fabricated hybrid TRM-coated Fe3O4 nanoparticles loaded with indocyanine green (ICG) and imiquimod (R837) for combination therapy in breast cancer. Comprehensive characterization of the RIFe@TRM nanoplatform revealed the inherent properties of both cell types. Compared to bare Fe3O4 nanoparticles, RIFe@TRM nanoparticles exhibited remarkable cell-specific self-recognition for 4T1 cells in vitro, leading to significantly prolonged circulation life span and enhanced in vivo targeting capabilities. Furthermore, the biomimetic RIFe@TRM nanoplatform induced tumor necrosis through the Fenton reaction and photothermal effects, while R837 facilitated enhanced uptake of tumor-associated antigens, further activating CD8+ cytotoxic T cells to strengthen antitumor immunotherapy. Hence, RIFe@TRM nanoplatform demonstrated outstanding synergy in chemodynamic/immunotherapy/photothermal therapies, displaying significant inhibition of breast tumor growth. In summary, this study presents a promising biomimetic nanoplatform for effective treatment of breast cancer.

Selenium can regulate the differentiation and immune function of human dendritic cells.

Selenium is an essential trace element that can regulate the function of immnue cells via selenoproteins. However, the effects of selenium on human dendritic cell (DCs) remain unclear. Thus, selenoprotein levels in monocytes, immature DCs (imDCs) and mature DCs (mDCs) treated with or without Na2SeO3 were evaluated using RT-PCR, and then the immune function of imDCs and mDCs was detected by flow cytometry, cell counting and the CCK8 assay. In addition, the effects of Se on cytokine and surface marker expression were investigated by RT-PCR. The results revealed different expression levels of selenoprotein in monocytes, imDCs and mDCs, and selenoproeins could be regulated by Se. Moreover, it was indicated that anti-phagocytic activity was improved by 0.1 µM Se, whereas it was suppressed by 0.2 µM Se in imDCs; The migration of imDCs and mDCs was improved by 0.1 µM Se, whereas their migration was inhibited by treatment with 0.05 or 0.2 µM Se; The mixed lymphocyte reaction of mDCs was improved by 0.1 µM Se, and it was inhibited by 0.05 and 0.2 µM Se. In addition, 0.1 µM Se improved the immune function of DCs through the regulation of CD80, CD86, IL12-p35 and IL12-p40. Wheres 0.05 and 0.2 µM Se impaired immune function of DCs by up-regulation of interleukin (IL-10) in imDCs and down-regulation of CD80, CD86, IL12-p35 and IL12-p40 in mDCs. In conclusion, 0.1 µM Se might improve the immune function of human DCs through selenoproteins.

Effect of Green Tea and (-)-Epigallocatechin Gallate on the Pharmacokinetics of Rosuvastatin.

BACKGROUND: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. OBJECTIVE: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. METHODS: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). RESULTS: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). CONCLUSION: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.

Hydrogen Peroxide Responsive Iron-Based Nanoplatform for Multimodal Imaging-Guided Cancer Therapy.

Cancer multimodal phototherapy triggered by hydrogen peroxide has attracted widespread attention as a dominating strategy to increase phototherapeutic efficiency. Herein, a hydrogen peroxide responsive iron oxide nanoplatform, with the diameter of about 50 nm, is fabricated to intracellularly trigger the Fenton reaction and achieve synergistic photodynamic therapy and photothermal therapy. The nanoplatform based on iron oxide nanoparticles is decorated with indocyanine green (ICG, photosensitizer) and hyaluronic acid (HA, targeting molecular) through electrostatic interaction, thus the as-prepared nanoplatform (IONPs-ICG-HA) exhibits excellent active targeting ability and biocompatibility. More importantly, it can effectively utilize the intratumoral overproduced hydrogen peroxide to generate reactive oxygen species for cancer cell killing via intracellular Fenton reactions. In vitro and in vivo experiments reveal that the IONPs-ICG-HA nanocomposites realize effective photoacoustic/photothermal/fluorescence imaging-guided phototherapy, leading to promising hydrogen peroxide responsive cancer theranostics.