Search

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB – possess a surface potential of −8 mV and a size of 150 nm – demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance. [ABSTRACT FROM AUTHOR]

Abstract Long-term live cell tracking is desirable and necessary to understand the dynamics and complexity of biological interactions in stem cells and cancer cells. Conventional live cells fluorescence trackers are generally non-degradable and are showing increased toxicity concerns during the long-term application. Previously we developed biodegradable fluorescent poly(citrate)-based hybrid elastomers for bone regeneration applications. Here, we fabricated the photoluminescent poly(citrate-siloxane) nanoparticles (PCSNPs) through an oil/water emulsion method and demonstrated their long-term live stem cells/cancer cells imaging applications. PCSNPs showed a uniform size distribution (mean diameter 120 nm) and highly stable dispersability (above 30 days) in various physiological medium, as well as excellent fluorescent properties and photostability. PCSNPs possess excellent cellular biocompatibility, which could be efficiently internalized by cells and selectively image the cell lysosome with a high photostability. Compared with commercial Cell Tracker™ Green and Cell Tracker™ Red, the adipose-derived mesenchymal stem cells or human hepatoma cells were stably labeled by PCSNPs for over 14 days as they grew and developed (7 passages). Additionally, PCSNPs efficiently tracked cells up to 7 days in vivo through a non-invasively way compared with 1 day of commercial tracker. This study demonstrates an important strategy to design biodegradable multifunctional delivery platforms for biomedical applications such as long-term bioimaging. Graphical abstract Unlabelled Image Highlights • Biodegradable PCS nanoparticles were fabricated through a facile emulsion technology. • PCSNPs showed a monodispersed size (120 nm) and highly stable dispersability. • PCSNPs exhibited excellent fluorescent properties and photostability. • PCSNPs possess excellent cellular biocompatibility and long term cell tracking. [ABSTRACT FROM AUTHOR]

Adhesion is a critical cellular process that contributes to migration, apoptosis, differentiation, and division. It is followed by the redistribution of cellular materials at the cell membrane or at the cell-surface interface for cells interacting with surfaces, such as basement membranes. Dynamic and quantitative tracking of changes in cell adhesion mass redistribution is challenging because cells are rapidly moving, inhomogeneous, and nonequilibrium objects, whose physical and mechanical properties are difficult to measure or predict. Here, we report a novel biosensor based microscopy approach termed Photonic Crystal Enhanced Microscopy (PCEM) that enables the movement of cellular materials at the plasma membrane of individual live cells to be dynamically monitored and quantitatively imaged. PCEM utilizes a photonic crystal biosensor surface, which can be coated with arbitrary extracellular matrix materials to facilitate cellular interactions, within a modified brightfield microscope with a low intensity non-coherent light source. Benefiting from the high sensitivity, narrow resonance peak, and tight spatial confinement of the evanescent field atop the photonic crystal biosensor, PCEM enables label-free live cell imaging with high sensitivity and high lateral and axial spatial-resolution, thereby allowing dynamic adhesion phenotyping of single cells without the use of fluorescent tags or stains. We apply PCEM to investigate adhesion and the early stage migration of different types of stem cells and cancer cells. By applying image processing algorithms to analyze the complex spatiotemporal information generated by PCEM, we offer insight into how the plasma membrane of anchorage dependent cells is dynamically organized during cell adhesion. The imaging and analysis results presented here provide a new tool for biologists to gain a deeper understanding of the fundamental mechanisms involved with cell adhesion and concurrent or subsequent migration events. [ABSTRACT FROM AUTHOR]

A bioorthogonal Raman reporter-embedded Au-core and polydopamine-shell nanoprobe was initially designed and synthesized for live cell surface-enhanced Raman scattering (SERS) imaging in Raman-silent region. The firstly synthetic bioorthogonal Raman reporter (E)-2- ((4-(phenylethynyl) benzylidene)amino)ethanethiol (PBAT) provided intense Raman signal at 2220cm-1 in Raman-silent region. And its synthetic method was environmentally benign, high yield and easy in operation. In addition, the hydrophobicity of PBAT led to slightly aggregation of gold nanoparticles, which enhance the SERS intensity of the nanoprobe through hot spots. Furthermore, owing to the remarkable biocompatibility of polydopamine (PDA), the SERS nanoprobe can be smoothly internalized into cancer cells to realize SERS imaging in Raman-silent region. Finally, the SERS mapping results confirmed that nanoprobe exhibited strong SERS signal intensity, excellent stability in complex biological environment and low toxicity inside live cancer cells. Therefore, the reporter-embedded core-shell nanoprobe has enormous potential of applications in biomedical diagnostics in the near future. Graphical abstractHighlights· One-step synthetic method of thiol and alkynyl contained bioorthogonal SERS reporter is environmentally benign, high yield and easy in operation. · Au@PBAT@PDA nanoparticles exhibit strong SERS signal intensity, excellent stability in complex biological environment. · Au@PBAT@PDA nanoparticles show good imaging results for live cancer cell SERS imaging in Raman-silent region. · The rich functional groups (i.e., catechol and amine) on PDA surface provide a broad platform for further modification in biomedical application. · A Raman-silent region nanoprobe was synthesized for live cell SERS imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • Knoevenagel condensation triggered synthesis of oxene based chemosensor (HyMa). Fusion of the intramolecular C-O bond along with electronic transitions have been validated via. SC-XRD as well as theoretically (DFT). • Discriminative spectroscopic alterations and electrochemical responses of HyMa towards different anionic species F−, CN– & HSO 4 − have been investigated with LOD of 94 ppb, 18 ppb and 38 ppb respectively. • HyMa has been exploited as a chemosensing tool for real water samples analysis with promising response and qualified recoveries. • The reversible recognition by Al3+ could formulate " Molecular Keypad Lock " to protect the confidential information at the molecular scale. • HyMa has been exploited for in vitro bio-imaging using triple negative breast cancer cell. A novel oxene based unusual sensory receptor (HyMa) has been synthesized via. Knoevenagel condensation triggered carbon-heteroatom (oxygen) intramolecular bond formation reaction at room temperature for discriminative detection of multi-analytes like HSO 4 −, CN– & F− by spectro-photometric alterations with profound selectivity with the detection limit of 38 ppb, 18 ppb & 94 ppb respectively. Examination of the sensing mechanism was exhaustively investigated through several spectroscopic means like 1H NMR, FT-IR, absorption and fluorescence spectra etc. In addition, quantum mechanical calculations like DFT and Loewdin spin population analyses also validated the rationality of the host–guest interaction. Apart from these, the reversible spectroscopic responses of HyMa towards F− and Al3+ can imitate several complex logic functions that in turn help in preparing molecular keypad lock. This molecular keypad lock has the potential to protect the confidential information at the molecular scale. Additionally, the MTT assay of HyMa showed low cytotoxicity and membrane permeability indicating its attractive capability for bio-imaging towards triple negative breast cancer. HyMa-coated test strips could also be employed towards on-site detection of these deadly contaminants via "Dip Stick" approach without help of any instrumentation. In addition, HyMa has also been exploited for quantitative determination of HSO 4 − from various real water samples. In a nutshell, detection of lethal contaminants like CN–, F− & HSO 4 − at ppb level with in vitro live cell imaging has been explored with proper photophysical characterisation and theoretical calculations with real field applications. [ABSTRACT FROM AUTHOR]

Polo-like kinase 1 (PLK1) is an important regulator of the cell cycle and is overexpressed in various solid and hematological malignancies. Small molecule inhibitors targeting PLK1, such as BI2536 or BI6727 (Volasertib) are a promising therapeutic approach in such malignancies. Here, we show a loss of specifically localized PLK1 in AML blasts in vivo , accompanied by mitotic arrest with transition into apoptosis, in bone marrow biopsies of AML patients after treatment with BI2536. We verify these results in live cell imaging experiments with the AML cell line HL-60, and demonstrate that non-neoplastic, immortalized lymphoblastoid cells are also sensitive to PLK1 inhibition. It is demonstrated that normal granulopoietic precursors have similar PLK1 expression levels as leukemic blasts. These results are in line with the adverse effects of PLK1 inhibition and underline the great potential of PLK1 inhibitors in the treatment of AML. [ABSTRACT FROM AUTHOR]

• A phenolphthalein-aminophenol (PFAP)-based chemosensor for Al3+ was synthesized. • PFAP showed a LOD of 1.5 µM and a fast response time of 10 s. • PFAP was used to detect Al3+ in the intracellular region of the A549 cancer cells. Monitoring of excess Al3+ and its selective detection in biological and environmental samples are important tasks for researcher due to its harmful effects. Herein, we present a phenolphthalein-aminophenol derived sensor (PFAP) for the selective fluorescent response of Al3+ in an "OFF-ON" mode over a pool of analytes including eighteen cations with striking greenish emission. It has a prominent limit of detection (LOD) value (1.5 µM), fast response time (10 s) for Al3+ detection. The complexation properties of PFAP with Al3+ ions were clarified by UV–vis, 1H & 13C NMR, HRMS, and FTIR spectroscopic experiments. The recognition mechanism of PFAP for Al3+working with chelation enhanced fluorescence (CHEF) and is verified with two model compounds PF and PFAN in the light of UV–vis, PL, TRPL, and NMR experiment. To check its applicability, easily prepared test paper and TLC strip of PFAP was produced for rapid and selective onsite detection of Al3+ ions. Bio-imaging application of PFAP in human lung cancer cell lines A549 demonstrated excellent results with negligible cytotoxicity and as an excellent marker to detect traces of Al3+ ion in a time-dependent as well as concentration-dependent manner. Actual sample analysis for Al3+ with the probe PFAP produces fruitful result. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: A new phenanthrene based chemosensor has been synthesized and investigated to act as highly selective fluorescence and visual sensor for Cu2+ ion with very low detection limit of 1.58nM; this has also been used to image Cu2+ in human cervical HeLa cancer cells. [Copyright &y& Elsevier]

• Herein, we report the synthesis and cation sensing properties of a new fluorescence reversible "turn-on" probe (HCBP). • HCBP selectively detects Al3+ in aqueous methanol medium at physiological pH with the enhancement of emission intensity. • Limit of detection (LOD) of the probe towards Al3+ is found to be in the order of 10-9 M. • Electronic structure and sensing mechanism of the probe is interpreted by DFT calculations. • The fluorescence imaging is performed using gastric cancer cells (AGS). A new coumarin based fluorescent switch (HCBP) has been fabricated which displays high selective sensing towards Al3+ among other metal cations at physiological pH. On gradual addition of Al3+ specifically, HCBP shows a brilliant "turn-on" emission enhancement of about ∼13-fold with about 50 nm red shift at 481 nm in MeOH/H 2 O (1/1, v/v) solution. The fluorescent switch is proven to be a reversible probe by addition of EDTA gradually into the HCBP-Al3+ solution. Detection limit as well as Binding constant values have been calculated and found to be in the order of 10−9 M and 103 M-1 respectively. DFT and TDDFT studies are conducted with the probe to establish a similarity between theoretical and experimental outcomes. We can also use this new fluorescent switch as a biomarker kit as it has shown a brilliant potential in the application of live cell imaging using gastric cancer cell (AGS cell). [ABSTRACT FROM AUTHOR]