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Robust Photodynamic Therapy Using 5-ALA-Incorporated Nanocomplexes Cures Metastatic Melanoma through Priming of CD4 <sup>+</sup> CD8 <sup>+</sup> Double Positive T Cells
摘要： Advanced melanoma can rarely be cured. Photodynamic therapy (PDT) readily eradicates the primary melanoma but has limited ability to destroy the spreading tumor cells unless supported by other combinative interventions to augment systemic antitumor immunity. Based on the previously synthesized penetration-enhancing biomaterials, a topically administered nanoformulation is developed, which profoundly assists 5-aminolevulinic acid (5-ALA) in circumventing skin barrier to be selectively delivered to tumor cells. After endocytosis, accumulated 5-ALA is efficiently metabolized to a photosensitizer protoporphyrin IX (PpIX) which stimulates a large production of cytotoxic reactive oxygen species (ROS) under illumination. Accompanied by the robust inflammatory responses followed by primary tumor destruction, CD4+CD8+ double positive T cells are highly boosted to harness host immunity to purge metastases in lymphoid organs. Compared with dacarbazine and programmed death 1 (PD-1) antibody, this treatment in advanced melanoma murine models, achieves a striking curable rate of 90% without melanoma prognostic markers LDH and S-100B detection, followed by a relapse-free survival rate of 83.33% in 300 days. Moreover, the cured mice’s immune system function recovers to an extent similar to healthy mice without prolonged or exaggerated inflammation. This study using the synergistic biomaterials approach may thus render 5-ALA-mediated PDT a potentially curative therapy for advanced melanoma in clinic.
关键词： advanced melanoma,CD4+CD8+ double positive cells,relapse-free survival,5-aminolevulinic acid,cure
更新于2025-11-25 10:30:42
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Surface Coatings Modulate the Differences in the Adhesion Forces of Eukaryotic and Prokaryotic Cells as Detected by Single Cell Force Microscopy
摘要： Single cell force microscopy was used to investigate the maximum detachment force (MDF) of primary neuronal mouse cells (PNCs), osteoblastic cells (MC3T3), and prokaryotic cells (Staphylococcus capitis subsp. capitis) from different surfaces after contact times of 1 to 5 seconds. Positively charged silicon nitride surfaces were coated with positively charged polyethyleneimine (PEI) or poly-D-lysine. Laminin was used as the second coating. PEI induced MDFs of the order of 5 to 20 nN, slightly higher than silicon nitride did. Lower MDFs (1 to 5 nN) were detected on PEI/laminin with the lowest on PDL/laminin. To abstract from the individual cell properties, such as size, and to obtain cell type-specific MDFs, the MDFs of each cell on the different coatings were normalized to the silicon nitride reference for the longest contact time. The differences in MDF between prokaryotic and eukaryotic cells were generally of similar dimensions, except on PDL/laminin, which discriminated against the prokaryotic cells. We explain the lower MDFs on laminin by the spatial prevention of the electrostatic cell adhesion to the underlying polymers. However, PEI can form long flexible loops protruding from the surface-bound layer that may span the laminin layer and easily bind to cellular surfaces and the small prokaryotic cells. This was reflected in increased MDFs after two-second contact times on silicon nitride, whereas the two-second values were already observed after one second on PEI or PEI/laminin. We assume that the electrostatic charge interaction with the PEI loops is more important for the initial adhesion of the smaller prokaryotic cells than for eukaryotic cells.
关键词： prokaryotic cells,poly-D-lysine,silicon nitride,laminin,cell adhesion,single cell force microscopy,surface coatings,polyethyleneimine,eukaryotic cells,maximum detachment force
更新于2025-11-21 11:24:58
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Cell Imaging Using Two-Photon Excited CdS Fluorescent Quantum Dots Working within the Biological Window
摘要： In recent years, two-photon excited semiconductor quantum dots (QDs) have been the subject of intense investigation due to their long excitation wavelength which helps to achieve deeper penetration and higher image resolution in optical bioimaging. In this paper, water-soluble CdS QDs were synthesized using a hydrothermal method and applied to human liver hepatocellular carcinoma (HepG2) cells. The first-principles calculation suggested that the S-rich defected structure contributes to a narrower band gap compared to the pristine structure. The resulting fluorescence wavelength was significantly red shifted, which was attributed to the deep defect states emission. The large Stokes shifts (> 200 nm) of the QDs can eliminate the possible cross-talk between the excitation light and the emission light. Two-photon induced red fluorescence emission can avoid overlapping with the autofluorescence emission of biological samples. The uptake and cell viability measurements of the HepG2 cells showed a good biocompatibility and a low toxicity of CdS QDs. Two-photon excited scanning microscopy images revealed that the HepG2 cells incubated with CdS QDs emitted bright red upconversion fluorescence and the fluorescence brightness was 38.2 times of that of the control group. These results support CdS QDs as a good candidate for application in cellular imaging.
关键词： two-photon absorption,CdS quantum dots,deep defect states,HePG2 cells,biological imaging
更新于2025-11-21 11:24:58
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ImmunoSERS microscopy for the detection of smooth muscle cells in atherosclerotic plaques
摘要： We investigated the suitability of immuno-SERS (iSERS) microscopy for imaging of smooth muscle cells (SMCs) in atherosclerotic plaques. Localization of SMCs is achieved by using SERS-labelled antibodies direct against alpha-smooth muscle actin (SMA). The staining quality of the false-colour iSERS images obtained by confocal Raman microscopy with point mapping is compared with wide-field immunofluorescence images. Both direct (labelled primary antibody) and indirect iSERS staining (unlabelled primary and labelled secondary antibody) techniques were employed. Direct iSERS staining yields results comparable to indirect IF staining, demonstrating the suitability of iSERS in research on atherosclerosis and paving the way for future multiplexed imaging experiments.
关键词： ImmunoSERS microscopy,Smooth muscle cells (SMCs),Atherosclerosis,Direct/indirect staining
更新于2025-11-21 11:24:58
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Fabrication of gold-silver core-shell nanoparticles for performing as ultrabright SERS-nanotags inside human ovarian cancer cells
摘要： This paper presents the fabrication and characterization of new gold-silver core-shell nanoparticles labeled with para-mercaptobenzoic acid (4MBA) molecules and demonstrates their use as SERS-nanotags with ultra-bright traceability inside cells and ability to convey spectrally-coded information about the intracellular pH by means of Surface-Enhanced Raman Spectroscopy (SERS). Unlike to previous reported studies, our fabrication procedure includes in the first step the synthesis of chitosan-coated gold nanoparticles as a seed material with subsequent growing of a silver shell. The bimetallic core-shell structure is revealed by transmission electron microscopy (TEM), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM), energy-dispersive X-ray elemental mapping (EDX) and the presence of two interacting localized surface plasmon resonance (LSPR) modes in UV-Vis extinction spectrum. The high SERS activity and sensitivity of as fabricated 4MBA-chit-Au-AgNPs nano-constructs to different pH in solution is investigated under 532 and 633 nm laser lines excitation. Next, in view of future studies in cancer diagnosis, the in vitro antiproliferative effects of SERS-nanotags against human ovarian adenocarcinoma cells (NIH:OVCAR-3) are evaluated. The capacity to operate as bright SERS nanotags with precise localization at a single cell level as well as intracellular pH indicators is clearly demonstrated by performing cell imaging under scanning confocal Raman microscopy.
关键词： core-shell nanoparticles,pH sensors,ovarian cancer cells,chitosan,SERS tags
更新于2025-11-21 11:24:58
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AIP Conference Proceedings [Author(s) PROCEEDINGS OF THE 3RD INTERNATIONAL CONFERENCE ON AUTOMOTIVE INNOVATION GREEN ENERGY VEHICLE: AIGEV 2018 - Kuantan, Malaysia (25–26 July 2018)] - Chemical bath deposition of In2S3 thin films as promising material and buffer layer for solar cells
摘要： The copper(I) and indium thin films are obtained by chemical bath deposition (CBD). Their elemental composition and microstructure were particularly studied by means of the x-ray photoelectron spectroscopy (XPS). The change in the surface microstructure of thin films depending on the temperature and the composition of reaction bath were determined by means of scanning electron microscopy (SEM).
关键词： chemical bath deposition,solar cells,thin films,buffer layer,In2S3
更新于2025-11-21 11:20:48
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An opsin 5–dopamine pathway mediates light-dependent vascular development in the eye
摘要： During mouse postnatal eye development, the embryonic hyaloid vascular network regresses from the vitreous as an adaption for high-acuity vision. This process occurs with precisely controlled timing. Here, we show that opsin 5 (OPN5; also known as neuropsin)-dependent retinal light responses regulate vascular development in the postnatal eye. In Opn5-null mice, hyaloid vessels regress precociously. We demonstrate that 380-nm light stimulation via OPN5 and VGAT (the vesicular GABA/glycine transporter) in retinal ganglion cells enhances the activity of inner retinal DAT (also known as SLC6A3; a dopamine reuptake transporter) and thus suppresses vitreal dopamine. In turn, dopamine acts directly on hyaloid vascular endothelial cells to suppress the activity of vascular endothelial growth factor receptor 2 (VEGFR2) and promote hyaloid vessel regression. With OPN5 loss of function, the vitreous dopamine level is elevated and results in premature hyaloid regression. These investigations identify violet light as a developmental timing cue that, via an OPN5–dopamine pathway, regulates optic axis clearance in preparation for visual function.
关键词： Hyaloid regression,Vascular development,Dopamine,VEGFR2,Light-dependent,Eye,Opsin 5,Retinal ganglion cells
更新于2025-11-21 11:20:42
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Stable Sn/Pb-Based Perovskite Solar Cells with a Coherent 2D/3D Interface
摘要： Low-band-gap metal halide perovskite semiconductor based on mixed Sn/Pb is a key component to realize high-ef?ciency tandem perovskite solar cells. However, the mixed perovskites are unstable in air due to the oxidation of Sn2+. To overcome the stability problem, we introduced N-(3-aminopropyl)-2-pyrrolidinone into the CH3NH3Sn0.5Pb0.5IxCl3-x thin ?lm. The carbonyl group on the molecule interacts with Sn2+/Pb2+ by Lewis acid coordination, forming vertically oriented 2D layered perovskite. The 2D phase is seamlessly connected to the bulk perovskite crystal, with a lattice coherently extending across the two phases. Based on this 2D/3D hybrid structure, we assembled low-band-gap Sn-based perovskite solar cells with power conversion ef?ciency greater than 12%. The best device was among the most stable Sn-based organic-inorganic hybrid perovskite solar cells to date, keeping 90% of its initial performance at ambient condition without encapsulation, and more than 70% under continuous illumination in an N2-?lled glovebox for over 1 month.
关键词： power conversion efficiency,2D/3D interface,stability,Sn/Pb-based,perovskite solar cells
更新于2025-11-21 11:18:25
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Coordination geometry-induced optical imaging of <scp>l</scp> -cysteine in cancer cells using imidazopyridine-based copper( <scp>ii</scp> ) complexes
摘要： Overexpression of cysteine cathepsins proteases has been documented in a wide variety of cancers, and enhances the L-cysteine concentration in tumor cells. We report the synthesis and characterization of copper(II) complexes [Cu(L1)2(H2O)](SO3CF3)2, 1, L1 = 3-phenyl-1-(pyridin-2-yl)imidazo[1,5-a]pyridine, [Cu(L2)2(SO3CF3)]SO3CF3, 2, L2 = 3-(4-methoxyphenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine, [Cu(L3)2(H2O)](SO3CF3)2, 3, L3 = 3-(3,4-dimethoxy-phenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine and [Cu(L4)2(H2O)](SO3CF3)2, 4, L4 = dimethyl-[4-(1-pyridin-2-yl-imidazo[1,5-a]pyridin-3-yl)phenyl]amine as 'turn-on' optical imaging probes for L-cysteine in cancer cells. The molecular structure of complexes adopted distorted trigonal pyramidal geometry (τ, 0.68–0.87). Cu–Npy bonds (1.964–1.989 ?) were shorter than Cu–Nimi bonds (2.024–2.074 ?) for all complexes. Geometrical distortion was strongly revealed in EPR spectra, showing gk (2.26–2.28) and Ak values (139–163 × 10?4 cm?1) at 70 K. The d–d transitions appeared around 680–741 and 882–932 nm in HEPES, which supported the existence of five-coordinate geometry in solution. The Cu(II)/Cu(I) redox potential of 1 (0.221 V vs. NHE) was almost identical to that of 2 and 3 but lower than that of 4 (0.525 V vs. NHE) in HEPES buffer. The complexes were almost non-emissive in nature, but became emissive by the interaction of L-cysteine in 100% HEPES at pH 7.34 via reduction of Cu(II) to Cu(I). Among the probes, probe 2 showed selective and efficient turn-on fluorescence behavior towards L-cysteine over natural amino acids with a limit of detection of 9.9 × 10?8 M and binding constant of 2.3 × 105 M?1. The selectivity of 2 may have originated from a nearly perfect trigonal plane adopted around a copper(II) center (～120.70°), which required minimum structural change during the reduction of Cu(II) to Cu(I) while imaging Cys. The other complexes, with their distorted trigonal planes, required more reorganizational energy, which resulted in poor selectivity. Probe 2 was employed for optical imaging of L-cysteine in HeLa cells and macrophages. It exhibited brighter fluorescent images by visualizing Cys at pH 7.34 and 37 °C. It showed relatively less toxicity for these cell lines as ascertained by the MTT assay.
关键词： optical imaging,cancer cells,turn-on fluorescence,imidazopyridine,L-cysteine,Copper(II) complexes
更新于2025-11-21 11:08:12
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Effects of Cytokine Activation and Oxidative Stress on the Function of the Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells
摘要： PURPOSE. In several retinal complications, such as age-dependent macular degeneration (AMD), oxidative stress is increased and cytokine level is elevated. These are shown to alter the activation and expression of matrix metalloproteinase (MMP) both in human primary and immortalized retinal pigment epithelial (RPE) cells. However, the effects on human embryonic stem cell (hESC)–derived RPE cells remain to be elucidated. METHODS. The mature hESC-RPE cells were exposed to inflammatory cytokines (IFN-γ or TNF-α) for 24 hours or oxidative stress (H2O2) for 1 hour. Effects on barrier properties were analyzed with transepithelial electrical resistance (TEER), the expression of MMP-1, MMP-2, MMP-3, MMP-9, collagen I, and collagen IV genes with quantitative RT-PCR, and the expression of MMP-1 and MMP-3 proteins with Western blot or ELISA, respectively. Also, activation and secretion of MMP-2 and -9 proteins were analyzed with zymography. RESULTS. In normal state, mature hESC-RPE cells expressed MMP-1, -2, -3, and -9 genes in low levels, respectively. Tumor necrosis factor-α increased MMP-1 and -2 gene expression, and H2O2 increased MMP-3 and -9 gene expression. Zymography revealed IFN-γ– and TNF-α–induced secretion of MMP-2 and high-molecular-weight species of MMP (HMW MMP), but H2O2 decreased their secretion. Furthermore, TNF-α and H2O2 significantly decreased barrier properties. CONCLUSIONS. Here, cytokines induced the MMP-1 and -2 gene and protein expression. Also, H2O2 induced MMP-3 and -9 gene expression, but not their protein secretion. These data propose that under oxidative stress and cytokine stimuli, mature hESC-RPE cells resemble their native counterpart in the human eye in regard to MMP secretion and expression and could be used to model retinal disorders involving alterations in MMP activity such as AMD, diabetic retinopathy, or proliferative vitreoretinopathy in vitro.
关键词： matrix metalloproteinase,MMP,stem cells,retinal pigment epithelium
更新于2025-11-21 11:08:12