Enhanced Antitumor Efficacy of Novel Biomimetic Platelet Membrane-Coated Tetrandrine Nanoparticles in Nonsmall Cell Lung Cancer.

Nonsmall cell lung cancer (NSCLC) remains one of the leading causes of cancer-related death worldwide, posing a serious threat to global health. Tetrandrine (Tet) is a small molecule in traditional Chinese medicine with proven primary efficacy against multiple cancers. Although previous studies have demonstrated the potential anticancer effects of Tet on NSCLC, its poor water solubility has limited its further clinical application. Herein, a novel nanoparticle-based drug delivery system, platelet membrane (PLTM)-coated Tet-loaded polycaprolactone-b-poly(ethylene glycol)-b-polycaprolactone nanoparticles (PTeNPs), is proposed to increase the potency of Tet against NSCLC. First, tetrandrine nanoparticles (TeNPs) are created using an emulsion solvent evaporation method, and biomimetic nanoparticles (PTeNPs) are prepared by coating the nanoparticles with PLTMs. When coated with PLTMs, PTeNPs are considerably less phagocytized by macrophages than Tet and TeNPs. In addition, compared with Tet and TeNPs, PTeNPs can significantly inhibit the growth and invasion of NSCLC both in vitro and in vivo. With reliable biosafety, this drug delivery system provides a new method of sustained release and efficient anticancer effects against NSCLC, facilitating the incorporation of Tet in modern nanotechnology.

Berberine Modulates Macrophage Activation by Inducing Glycolysis.

Classical activation of macrophage and monocyte differentiation induced by ß-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.