Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. The "Terminator" in the science fiction film is a cybernetic organism with living tissue over a metal endoskeleton, which inspired us to develop natural-killer-cell-mimic nanorobots with aggregation-induced emission (AIE) characteristics (NK@AIEdots) by coating a natural kill cell membrane on an AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owing to the AIE and soft-matter characteristics of PBPTV, as-prepared NK@AIEdots maintained a superior NIR-II brightness (quantum yield ∼7.9% in water) and good biocompatibility. Besides, they can serve as a tight junction (TJ) modulator to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to form an intercellular "green channel" to help them to cross the blood−brain barrier (BBB) silently. Furthermore, they can initiatively accumulate in glioblastoma cells in the complex brain matrix for highcontrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these NK@AIEdots under the NIR light illumination. As far as we know, the quantum yield of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots showed great potential for BBB-crossing active delivery.
A time-resolved spectroscopic imaging system is built to study the fluorescence characteristics of nicotinamide adenine dinucleotide (NADH), an important metabolic coenzyme and endogenous fluorophore in cells. The system provides a unique approach to measure fluorescence signals in different cellular organelles and cytoplasm. The ratios of free over protein-bound NADH signals in cytosol and nucleus are slightly higher than those in mitochondria. The mitochondrial fluorescence contributes about 70% of overall cellular fluorescence and is not a completely dominant signal. Furthermore, NADH signals in mitochondria, cytosol, and the nucleus respond to the changes of cellular activity differently, suggesting that cytosolic and nuclear fluorescence may complicate the well-known relationship between mitochondrial fluorescence and cellular metabolism.
Gastric cancer shows the highest invasive and metastasis features, especially lymph metastasis, which is closely associated with poor prognosis of gastric cancer. Although there is evidence that interleukin-6 (IL-6) can promote gastric cancer progression, the underlying specific mechanisms and the mechanisms of gastric cancer lymphangiogenesis are largely unknown. In the present study, we explore whether IL-6 could promote the proliferation and invasion activity of gastric cancer cells, and whether IL-6 mediating VEGF-C production affected the lymphangiogenesis in gastric cancer cells. Our results revealed that IL-6 and its receptors (IL-6 and gp130) are broadly expressed in various gastric cancer cell lines including SGC-7901, MGC, MKN-28 and AGS. Exogenous IL-6 increased the ability of gastric cancer cell proliferation and invasion, which could be weakened by AG490. in addition, exogenous IL-6 promoted the VEGF-C production of gastric cancer cells and the lymphangiogenesis of HDLECs. As we expected, AG490 was able to reduce these effects. Western blot analysis showed that IL-6 increased JKA, STAT3, p-STAT3 and VEGF-C protein levels in the gastric cancer cells. However, the JKA, STAT3, p-STAT3 and VEGF-C protein expression levels were inhibited by AG490. Our data suggested that IL-6 mediates the singnal pathway of JAK-STAT3-VEGF-C promoting the growth, invasion and lymphangiogenesis in gastric cancer. Thus, IL-6 and its related signal pathways may be a promising target for treatment of gastric cancer growth and lymphangiogenesis.
We discovered that hemoglobin emits high energy Soret fluorescence when two-photon excited by the visible femtosecond light sources. The unique spectral and temporal characteristics of hemoglobin fluorescence were measured by using a time-resolved spectroscopic detection system. The high energy Soret fluorescence of hemoglobin shows the spectral peak at 438 nm with extremely short lifetime. This discovery enables two-photon excitation fluorescence microscopy to become a potentially powerful tool for in vivo label-free imaging of blood cells and vessels.
A successful strategy for the design of ultrabright red luminogens with aggregation-induced emission (AIE) features is reported. The AIE dots can be utilized as efficient fluorescent probes for in vivo deep-tissue imaging with high penetration depth and high contrast.
Lipopolysaccharide (LPS) exists in the outer membrane of Gram-negative bacteria. Colorectal normal epithelium and colorectal cancer cells in situ are continuously exposed to LPS from intestinal bacteria, while little is known about the influence of LPS on colorectal cancer progression and metastasis. In this study, we investigated the potential role of LPS on colorectal cancer progression and metastasis as well as the underlying mechanisms. We measured higher LPS concentration in colorectal cancer tissues and even higher LPS concentration in colorectal cancer tissues with lymph node metastasis. LPS significantly enhanced cancer cell motility and promoted human dermal lymphatic endothelial cells' (HDLECs') capacity of tube-like formation in vitro, as well as accelerates lymphangiogenesis and lymph node metastasis in nude mice. Furthermore, we demonstrated LPS notably increased the expression of VEGF-C in a time-dependent and concentration-dependent manner. VEGF-C is a key regulator for lymphangiogenesis and lymph node metastasis. By constructing lentivirus-mediated shVEGF-C cells, VEGF-C down-regulation suppressed LPS' promotive effect on cancer cell motility and HDLEC tube-like formation capacity. In addition, we found TLR4- NF-κB/JNK signal pathways were important for LPS to increase VEGF-C expression. All these result suggested a critical role for LPS in migration, invasion, lymphangiogenesis and lymph node metastasis of colorectal cancer, providing evidence that LPS increased VEGF-C secretion to promote cell motility and lymphangiogenesis via TLR4- NF-κB/JNK signaling.
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