Meizhen Yin

A fluorescent core-shell dendritic macromolecule specifically stains the extracellular matrix

The extracellular cell matrix (ECM) surrounds cells and plays important roles in many aspects of cellular fate, including cell migration, stem cell differentiation, and cancer progression. So far, there is no fluorescent dye to directly visualize the ECM network. Here we present a positively charged fluorescent core-shell dendritic macromolecule containing multiple -NH2 groups which specifically binds to highly negatively charged ECM components. Due to its advantageous optical properties and biological specificity, the dye is useful as a routine tool to label the ECM in life science research.

Fluorescent Core/Shell Nanoparticles for Specific Cell-Nucleus Staining†

The highly fluorescent perylene-3,4,9,10-tetracarboxdiimide (PDI) chromophore is a popular dye and pigment because of its excellent chemical, thermal, and photochemical stability. Due to these outstanding properties, there have been several successful applications of PDI chromophores in various fields. Water-soluble and fluorescent PDI dyes have been used in biological applications such as the in vitro staining of cells and proteins. The combination of water solubility and high fluorescence quantum yield still represents a challenging goal since PDI dyes have a strong tendency to form aggregates in aqueous solution even at very low concentrations. Water solubility and high fluorescence quantum yields of ionic PDIs were obtained by introducing positively or negatively charged substituents into the bay region of the chromophore. Although these ionic PDIs penetrate the cytoplasmic membrane of living cells, the synthesis of PDIs with specific binding properties to subcellular compartments has not yet been achieved. Recently, the preparation of core/shell nanoparticles with high structural perfection, water-solubility, and biocompatibility has been reported. However, the synthesis and biological characterization of fluorescent core/shell nanoparticles with specific biological applications have not been demonstrated. Herein we describe a novel water-soluble, negatively charged PDI derivative that specifically labels the cell nucleus by strong binding to positively charged nuclear proteins, thus allowing their application as a fluorescent dye in pathological and histochemical studies. The core/shell nanoparticle (Figure 1, P1) consists of a central PDI chromophore, a rigid first-generation polyphenylene dendrimer scaffold for suppressing aggregation of the central PDI chromophore in aqueous media and a polymer shell with multiple carboxylic acid groups for inducing water solubility and biological specificity. The synthetic strategy towards P1 is shown in Scheme 1, starting from the previously

Novel Fluorescent Core-Shell Nanocontainers for Cell Membrane Transport

The synthesis and characterization of novel core-shell macromolecules consisting of a fluorescent perylene-3,4,9,10-tetracarboxdiimide chromophore in the center surrounded by a hydrophobic polyphenylene shell as a first and a flexible hydrophilic polymer shell as a second layer was presented. Following this strategy, several macromolecules bearing varying polymer chain lengths, different polymer shell densities, and increasing numbers of positive and negative charges were achieved. Because all of these macromolecules reveal a good water solubility, their ability to cross cellular membranes was investigated. In this way, a qualitative relationship between the molecular architecture of these macromolecules and the biological response was established.

Dendritic Star Polymers for Efficient DNA Binding and Stimulus-Dependent DNA Release

Water-soluble core-shell star polymers consisting of a dendritic polyphenylene core and an outer shell containing a defined number of amino groups have been synthesized via atom transfer radical polymerization (ATRP). All macromolecules efficiently interacted with a diverse set of DNA fragments, and stable complexes were formed and visualized by atomic force microscopy. The observed tight binding of DNA, which was found in the sub-nanomolar range, was mainly attributed to strong electrostatic interactions. Complex stoichiometries between the polyelectrolytes were controlled via the number of amino groups of the star polymers, and well-defined nanoscopic architectures were formed. DNA was released from the complexes after treatment with high concentrations of sodium chloride in aqueous solution. Such star polymers, which allow the binding and release of DNA, represent attractive candidates for the development of novel anion-exchange resins for DNA purification or as nonviral vector systems for gene delivery.

Terrylenediimide-Based Intrinsic Theranostic Nanomedicines with High Photothermal Conversion Efficiency for Photoacoustic Imaging-Guided Cancer Therapy

Activatable theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, the theranostic nanomedicines widely suffer from instability and complicated nanostructures, which hamper potential clinical applications. Herein, we demonstrated a terrylenediimide (TDI)-poly(acrylic acid) (TPA)-based nanomedicine (TNM) platform used as an intrinsic theranostic agent. As an exploratory paradigm in seeking biomedical applications, TDI was modified with poly(acrylic acid)s (PAAs), resulting in eight-armed, star-like TPAs composed of an outside hydrophilic PAA corona and an inner hydrophobic TDI core. TNMs were readily fabricated via spontaneous self-assembly. Without additional vehicle and cargo, the as-prepared TNMs possessed a robust nanostructure and high photothermal conversion efficiency up to approximately 41%. The intrinsic theranostic properties of TNMs for use in photoacoustic (PA) imaging by a multispectral optoacoustic tomography system and in mediating photoinduced tumor ablation were intensely explored. Our results suggested that the TNMs could be successfully exploited as intrinsic theranostic agents for PA imaging-guided efficient tumor PTT. Thus, these TNMs hold great potential for (pre)clinical translational development.

A multifunctional perylenediimide derivative (DTPDI) can be used as a recyclable specific Hg2+ ion sensor and an efficient DNA delivery carrier

Multifunctional dithioacetal-modified perylenediimide (DTPDI) is synthesized as a highly sensitive and selective fluorescent chemosensor for recyclable Hg2+ detection and an effective DNA carrier. The central PDI chromophore allows the tracing of cell uptake by fluorescence microscopy, dithioacetals enable the detection of Hg2+, and peripheral amine hydrochloride salts increase the water solubility and also serve as positive charges for noncovalent binding of negatively charged DNA. In addition to serve as a recyclable fluorescent probe for Hg2+ detection, DTPDI can be rapidly internalized into live cells with low cytotoxicity and high DNA delivery efficacy.

Functionalization of Self-Assembled Hexa-peri-hexabenzocoronene Fibers with Peptides for Bioprobing

A novel water-soluble hexa-peri-hexabenzocoronene (HBC) derivative with peripheral functional groups, which facilitates a two-step assembly process in water that includes fiber formation via pi stacking and subsequent peptide probing via electrostatic interactions, is reported. In the first step, the HBC derivative self-assembles into water-soluble red-fluorescent fibers that serve as templates for further functionalization with biomolecules. In the second assembly step, the peripheral functional groups bind green-fluorescent fluorescein-conjugated peptides, leading to the formation of well-defined fibers that were visualized as dual-color fibers in double-fluorescence imaging.

pH-sensitive unimolecular fluorescent polymeric micelles: from volume phase transition to optical response

Unimolecular fluorescent micelles of star polyelectrolytes with a perylenediimide core are very sensitive to changes in pH values. The pH-responsive behavior relies on the ionization or deionization of the star polyelectrolytes, which causes a reversible volume phase transition and optical response.

A Difunctional Squarylium Indocyanine Dye Distinguishes Dead Cells through Diverse Staining of the Cell Nuclei/Membranes

Functionalized fluorescent dyes have attracted great interest for the specific staining of subcellular organelles in multicellular organisms. A novel nanometer-sized water-soluble multi-functional squarylium indocyanine dye (D1) that contains four primary amines is synthesized. The dye exhibits good photostability, non-toxicity and biocompatibility. Isothermal titration calorimetry demonstrates that an affinity between D1 and DNA is higher than that between D1 and analogue of phospholipids. Analysis of circular dichroism spectra indicates that D1 targets to the DNA minor groove and aggregates to a helix. Because of the distinct affinity between the dye and subcellular organelles, the dye exhibits difunctional abilities to label the cell nuclei in fixed cells/tissue and the cell membranes in live cells/tissue. By combination of the two staining capabilities, the dye is further explored as a specific marker to distinguish apoptotic cells in live cells/tissue. The research opens a new way to design novel multifunctional dyes for life science applications.

Perylene-cored Star-shaped Polycations for Fluorescent Gene Vectors and Bioimaging

Two star polycations, poly(2-aminoethyl methacrylate) (PAEMA, P1) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA, P2), have been synthesized with perylene diimide (PDI) as the central fluorophore. (1)H NMR and (13)C NMR are used to confirm the successful synthesis of a macromolecular initiator. Using ATRP strategy, P1 and P2 are obtained with narrow molecular weight distribution. The star polymers have good fluorescence properties in aqueous solution, which provides fluorescent tracing and imaging during gene delivery. Both P1 and P2 can efficiently condense DNA into stable nanoparticles. Transfection studies demonstrate that P1 and P2 deliver DNA into live cells with higher efficiency and lower cytotoxicity than polyethylenimine (PEI, 25 kDa). P2 shows higher capacity for gene delivery than P1 due to its better buffering and faster rate of cellular internalization.